Highly Active Antiretroviral Therapy Research Articles

Some Coagulation and Haematological Parameters of Human Immunodeficiency Virus Positive Individuals Accessing Clinic in Haart Centers in Esan South-East Local Government Area of Edo State, Nigeria

Highly active antiretroviral therapy (HAART) has significantly reduced the scourge of Human Immunodeficiency Virus and its associated mortality, but systemic complications, haematological changes and other complications have been reported in patients receiving HAART (or ART).

Current insights and molecular docking studies of HIV-1 reverse transcriptase inhibitors.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).

Relationship among serum levels of IL-6, sIL-6R, s gp130 and CD126 on T-cell in HIV-1 infected and uninfected men participating in the Los Angeles Multi-Center AIDS Cohort Study.

Interleukin 6 (IL-6) activates cells through its unique heterodimeric signaling complex of IL-6 receptor (IL6R) subunit and interleukin 6 signal transducer β-subunit glycoprotein 130 (gp130). The objective of this study was to investigate associations among serum levels of IL-6, sIL-6R, sgp130 and relative fluorescence intensity (RFI) of the α-subunit of the IL-6 receptor (CD126) on T-cells of HIV-1 infected and uninfected men. Blood samples were obtained from 69 HIV-1-infected men on Highly Active Antiretroviral Therapy (HAART) with mean age of 49.1 and 52 HIV-1-uninfected with mean age of 54.3 years -. All men were participating in the Los Angeles Multi-Center AIDS Cohort Study (MACS). Serum levels of IL-6, sIL-6R, sgp130 were measured by enzyme-linked immunoassays and T-cell phenotypic analysis and RFI of CD126 on CD4+ and CD8+ by flow cytometry. Mean serum levels of IL-6, sIL6R, sgp130 and of CD126 RFI on CD4+ were 4.34 pg/mL, 39.3 ng/mL, 349 ng/mL and 526 RFI respectively for HIV-1-infected men and 2.74 pg/mL, 41.9 ng/mL, 318 ng/mL and 561 RFI respectively for HIV-1-uninfected men. The mean serum concentrations of IL-6, sIL-6R in HIV-1-infected and uninfected men were not significantly different (p>0.05). There was a positive correlation between plasma HIV-1 RNA and the levels of IL-6 (p<0.001), sIL6R (p = 0.002) but no correlation with sgp130 (p = 0.339). In addition, there was a negative correlation between serum levels of IL-6 with RFI of CD126 on CD4+ (p = 0.037) and a positive correlation between serum levels of sgp130 (p = 0.021) and sIL-6R in HIV-1-infected men. Knowledge of biological variation, differences in the blood levels of biomarkers among healthy individuals and individuals experiencing illness, are very important for selection of appropriate tests for stage and progression of disease. Our data suggest no correlation among IL-6, and sIL-R6, in the treated phase of HIV-1 infection. The action and blood level of IL-6 and its receptors may be different at each stage of a disease progression.

Effect of immunological non-response on incidence of Non-AIDS events in people living with HIV: A retrospective multicenter cohort study in Taiwan.

People living with HIV (PLWH) are susceptible to non-AIDS-related events, particularly those with immunological nonresponses (INRs) to highly active antiretroviral therapy (HAART). This study assessed the association of INRs with incident non-AIDS-related events among PLWH. This multicenter retrospective cohort study enrolled PLWH who had newly diagnosed stage 3 HIV and received HAART between January 1, 2008, and December 31, 2019. The patients were divided into two groups according to their immunological responses on the 360th day after HAART initiation: INR and non-INR groups. Cox regression and sensitivity analyses were conducted to estimate the effects of INRs on overall and individual categories of non-AIDS-related events (malignancies, vascular diseases, metabolic disorders, renal diseases, and psychiatric disorders). Patient observation started on the 360th day after HAART initiation and continued until February 28, 2022, death, or an outcome of interest, whichever occurred first. Among the 289 included patients, 44 had INRs. Most of the included patients were aged 26-45 years (69.55%) and were men who have sex with men (89.97%). Many patients received HIV diagnoses between 2009 and 2012 (38.54%). INRs (vs. non-INRs) were associated with composite non-AIDS-related events (adjusted hazard ratio [aHR]=1.80; 95% confidence interval [CI]: 1.19-2.73) and metabolic disorders (aHR=1.75; 95% CI: 1.14-2.68). Sensitivity analyses revealed consistent results for each Cox regression model for both composite non-AIDS-related events and metabolic diseases. Clinicians should be vigilant and implement early intervention and rigorous monitoring for non-AIDS-related events in PLWH with INRs to HAART.

Anemia in HIV Patients Attending Highly Active Antiretroviral Therapy Clinic at Hoima Regional Referral Hospital: Prevalence, Morphological Classification, and Associated Factors.

To determine the prevalence of anemia, the morphological classification and to assess the factors associated with anemia among HIV patients attending Highly Active Antiretroviral Therapy (HAART) clinic at Hoima Regional Referral Hospital. This was a cross-sectional study among 340 participants attending the HAART clinic at Hoima Regional Referral Hospital. Participants were recruited using a simple random sampling technique. A complete blood count (CBC) was performed using the Sysmex XN-550 hematology analyzer. Thick films were made and examined for malaria parasites, while thin films were examined for the morphological classification of anemia. Bivariate and multivariate logistic analyses were conducted using SPSS (version 23). Out of the 340 study participants, 255 (75%) were females, and the median age was 39 years (range: 6-76 years). The overall prevalence of anemia among the study participants was 16.8% (95% CI 13.1-21.1). Normocytic normochromic anemia was the most prevalent form of anemia (47.4%). The logistic regression at multivariate analysis showed that age groups (18-27 years, p = 0.017; 28-37 years, p = 0.005; and ≥38 years, p = 0.009), divorced marital status (p = 0.024), the presence of chronic disease (p = 0.010), a family history of anemia (p = 0.007), and the presence of malaria in the past one month (p = 0.001), presence of opportunistic infection (OR = 58, p = 0.000), use of antihelminthic drug in the past 3 months (OR = 0.10, p = 0.003) and unsuppressed viral load (OR = 10.74, p = 0.000) had a significant association with anemia. Anemia is prevalent in HIV/AIDS patients who receive treatment at Hoima Regional Referral Hospital. Age, marital status, the presence of chronic illnesses, a family history of anemia, experiencing malaria in the past 3 months, the presence of opportunistic infections, the use of antihelminthic drugs in the past 3 months, and an unsuppressed viral load were significantly associated with anemia.

Assessments of viral load and haematological parameters in HIV patients on HAART in Ilorin, Kwara state

Human immune deficiency virus (HIV) infection represents the most common cause of acquired immune deficiency and leads to clinical disease referred to as Acquired Immune Deficiency Syndrome (AIDS). Highly active antiretroviral therapies (HAART) are the gold standard for the management of HIV disease. Viral load indicates that treatment is effective. A high viral load in a person on treatment indicates either that the medication is not being taken properly or that the virus is becoming resistant to the medication. This is a comparative study aimed at assessing the Viral load count and haematological parameters. 120 HIV positive individual and 40 HIV negative subjects were recruited for this study,while haematological parameters were carried out using Sysmex KX-21 analyser. Results was analyzed using SPSS version 20. .Our result shows the following mean absolute counts of haematological parameters; lymphocyte count of HIV positive persons to be 1.42±1.82, Neutrophil 1.64±2.80, Monocyte 0.07±0.08, Basophil 0.05±0.06 Eosinophil 1.71±3.42 while the mean value of TWBC 5.130±1.43, RBC 3.97±0.48, HB 11.41±1.65, MCV 87.054±15.59 and MCHC MCHCf/l, compared to 0.78±0.08, 1.10±0.32, 0.06±0.02, 0.01±0.01 and 1.14±3.42 respectively among the HIV negative individual. In conclusion, we found that the use of antiretroviral drugs could positively or negatively affect haematological parameters, depending on the choice of combination used.

Atypical perianal and buttocks epidermal-dermal necrosis in Human Monkeypox. Histopathological study of the lesion in Peru

We report the histopathological study of a large, black, crusted lesion with symmetrical distribution in both buttocks and perineum, never described, in a man who has sex with men (MSM) and proctitis associated with Human Monkey Pox Virus (hMPXV) and HIV-AIDS infection never treated. A 39-year-old male, homosexual, HIV-AIDS without Highly Active Antiretroviral Therapy (HAART), was admitted to a hospital in Lima, Peru, with papulopustular lesions on the body and perianal area. Days later, a large, crusty, black lesion with a symmetrical distribution appeared on the buttocks and perineum. The tissue culture was negative. Wedge biopsy of the lesion showed typical MPXV cytopathogenics lesions in addition to fibrin micro thrombosis in the underlying papillary dermis. The histopathological findings of the scabby and black lesion are the classic ones described by Stagles, except for the phenomenon of fibrin micro thrombosis in the papillary dermis, a novel cytopathogenic effect of MPXV with clinical relevance (epidermal-dermal necrosis).

Evaluation of Thyroid Function of HIV Patients in Umunze, Anambra State, Nigeria

Background: Abnormal thyroid function tests have been detected at various phases in people living with Human immunodeficiency virus (HIV) and the effect of highly active antiretroviral therapy (HAART) not well understood. However, there is insufficient study among Nigerians living with HIV.&#x0D; Objective: This study is aimed to determine thyroid hormones in HIV positive individuals compared with HIV negative individuals in Umunze, Anambra State, Nigeria.&#x0D; Materials and Methods: This cross-sectional study was carried out over a period of six months among 95 HIV positive and 30 HIV negative individuals attending USAID/FHI clinic of Immaculate Heart Hospital in Umunze, Nigeria. The subjects were divided into three groups on the basis of HAART (those on HAART [48] – GROUP 1, HAART naïve [47] – GROUP 2 and Control [30] – GROUP 3). The subjects were interviewed, examined and blood sample collected for determination of thyroid function parameters which include thyroid stimulating hormone (TSH), free triiodothyronine (fT3), triiodothyronine (T3), free thyroxine (fT4), and thyroxine (T4).&#x0D; Results: Among the 125 subjects recruited for the study 67.2% were females and 32.8% males. The mean levels of TSH and fT3 was found to be higher in group 1 subjects than in group 2 and the group 3 subjects. The mean level of T4 was significantly higher in group 2 subjects than group 1 and the group 3 subjects. The level of T3 was significantly lower in control subjects in comparison to both HAART and non-HAART subjects. Primary hypothyroidism is the commonest pattern of thyroid dysfunction among the HIV positive patients followed by isolated low fT4.&#x0D; Conclusion: Serum levels of thyroid hormones as shown in this study may be used as baseline periodic markers during antiretroviral therapy while people living with HIV may benefit from supplementation if appropriate. There is also need for a larger study to identify the risk factors for progression to overt thyroid disease in HIV infected subjects with thyroid autoimmunity.

The Prognosis of Progressive Multifocal Leukoencephalopathy in HIV/AIDS Patients Undergoing Highly Active Antiretroviral Treatment: A Systematic Review.

Progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system (CNS), is most commonly associated with advanced HIV infection. Although the severe neurological conditions - PML and progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS) - are linked to HIV, little is known about their characteristics in the era of established antiretroviral therapy (ART). The aim of this systematic review, which was performed by adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, was to determine the prognosis of PML in patients with HIV. We gathered and examined articles, including case-control and cohort studies, systematic reviews, and meta-analyses that were published between January 1, 2013, and May 2023. These articles were compiled from the following databases: Pubmed, Pubmed Central, Google Scholar, Wiley Library, and ScienceDirect. A total of 519 records were found from these databases for our systematic review after applying the proper filters. They were then further screened and put through quality appraisal tools, which ultimately led to the selection of 10 articles for the final analysis. This research offers crucial insights into the clinical consequences of PML in HIV patients receiving highly active antiretroviral therapy (HAART).

The cognitive remediation of attention in HIV-associated neurocognitive disorders (HAND): A meta-analysis and systematic review.

Background: Despite medical advances in Highly Active Antiretroviral Therapy (HAART), patients living with HIV continue to be at risk for developing HIV-associated neurocognitive disorders (HAND). The optimization of non-HAART interventions, including cognitive rehabilitation therapy (CRT), shows promise in reversing the impact of HAND. No data exist indicating the efficacy of CRT in remediating attention skills following neuroHIV. This paper presents a meta-analysis of randomised and non-randomised controlled trials (RCTs) to remediate attention skills following HIV CRT. Methods: The database search included literature from Google Scholar, ERIC, Cochrane Library, ISI Web of Knowledge, PubMed, PsycINFO, and grey literature published between 2013 and 2022. Inclusion criteria included studies with participants living with HIV who had undergone CRT intervention to remediate attention skills following neuroHIV. Exclusion criteria included case studies, non-human studies, and literature reviews. To assess study quality, including, randomisation, allocation concealment, participant and personnel blinding, the Cochrane Collaboration ratings system was applied. Results: A total of 14 studies met the inclusion criteria (n = 532). There were significant pre- to post-intervention between-group benefits due to CRT in the experimental group relative to control conditions for the remediation of attention skills following HIV acquisition (Hedges g = 0.251, 95% CI = 0.005 to 0.497; p < 0.05). No significant effects (p > 0.05) were demonstrated for subgroup analysis. Conclusions: To the author's knowledge, this is the first meta-analysis that exclusively analyses the remediation of attention skills in the era of HAART and neuroHIV, where all studies included participants diagnosed with HIV. The overall meta-analysis effect indicates the efficacy of CRT in remediating attention skills in HIV and HAND. It is recommended that future cognitive rehabilitation protocols to remediate attention skills should be context and population-specific and that they be supplemented by objective biomarkers indicating the efficacy of the CRT. Registration: Protocols.io (01/03/2023).

Multi-Clinical Factors Combined with an Artificial Intelligence Algorithm Diagnosis Model for HIV-Infected People with Bloodstream Infection.

Although highly active antiretroviral therapy (HA-ART) can effectively suppress the disease process in patients with acquired immunodeficiency syndrome (AIDS), opportunistic infections, mainly bloodstream infections (BSI), are still the main cause of death in people living with HIV. There is no effective diagnostic strategy for HIV-infected people with BSI. This study aimed to develop an AI diagnostic model with high sensitivity to improve the early detection of HIV-infected people with BSI. This study retrospectively analyzed the 40 clinical factors of 498 HIV-infected people (171 with BSI positive and 327 with BSI negative) who admitted to Wenzhou Central Hospital from September 2014 to July 2021. This study used the hospital information management system to collect the clinical characteristics, laboratory and imaging examination results, and clinical diagnosis of the two groups. The diagnostic results of all patients were in line with the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of AIDS (2021 Edition), and the BSI diagnosis was in line with the diagnostic criteria of sepsis and bacteremia in Practical Internal Medicine (13th Edition). On this basis, various risk prediction models were established by combining 8 artificial intelligence (AI) algorithms in the training set and validating the diagnosis performance in the testing set. The model with the best diagnostic performance was selected as the final diagnostic model. The clinical characteristics of HIV-infected people with BSI are atypical, and the pathogens in this area are mainly fungi. Ten risk factors were selected: low level of hemoglobin, CD4+T cell and platelets, high level of lactate dehydrogenase and blood urea nitrogen, splenomegaly, without ART treatment, strip shadow, nodular shadow, and shock. The combination of the ten risk factors, age, gender and the "svmRadial" model can identify the HIV-infected people with BSI from the HIV-infected people without BSI with an area under the curve of 0.916 and a sensitivity and specificity of 0.824 and 0.855, respectively. The model showed excellent performance in diagnosing HIV-infected people with BSI. Internal and external validation showed that the diagnosis model had high clinical application value.

Application of CRISPR-Cas9 for the Prevention and Treatment of HIV-1 Prevention

Human immunodeficiency virus, also known as HIV, is a virus that attacks the body’s immune system. As of today, the virus is prevalent, particularly across the United States and Sub-Saharan Africa [23]. There are treatments in place for the prevention of HIV, however, for those who are HIV/AIDS positive there’s still a long way to go in terms of developing treatments to cure the disease entirely. In this review, we will cover how CRISPR-Cas9 can be used to treat HIV-1 thereby overcoming limitations of existing treatments. For example, while highly active antiretroviral therapy (HAART) is used to suppress HIV’s replication process, it cannot cure HIV as it cannot target inactive HIV-1. CRISPR-Cas9 could treat latent HIV-1 infection by editing out the viral DNA in the host’s genome, removing the co-receptors of the host cell, genetically modifying HSC cells, and combining the use of CRISPR-Cas9 with “Shock and Kill.” However, while these methods of preventing and treating HIV-1 do show promise, they will need to be further developed with biological limitations in mind which will be covered in this review. In addition to biological limitations, moral and ethical concerns are present as CRISPR-Cas9 introduces designer babies with somatically edited genes, super-humans, and malignant mutations, these considerations will be covered in the discussion.

Long-term prognosis and overall mortality in patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.

Pursuing Dementia in People Living with HIV: Prevalence and Associated Factors

Introduction: The human immunodeficiency virus (HIV) is the leading cause of neurocognitive impairment in people over 40. The development of highly active antiretroviral therapy (HAART), the comprehension of disease pathogenesis, and the constant search for better life quality in people living with HIV have led to the HIV disease chronic evolution. Hence, it has been common to observe chronic diseases such as HIV-associated neurocognitive disorder (HAND). Unfortunately, the practitioner’s unfamiliarity with HAND screening and treatment has contributed to poor patient care. Methods: We evaluated 134 patients living with HIV and performed two tracking tests, the Mini-mental, which evaluates cortical dementia, and the International HIV Dementia Scale, which evaluates subcortical dementia. Results: We observed dementia associated with HIV (HAD) in 29 patients (prevalence of 21.6%; CI 95%: 15.0 – 29.6). The independent factors related to HAD in this study, with statistical significance, were age (RPaj 1.05; CI 1.00 – 1.09; p=0.033), TCD4+ nadir (RPaj 0.998; CI 95% 0.996 – 0.999; p=0.03), and more than two years of detectable HIV viral load (RPaj 2.35; CI 95% 1.27 – 4.33; p=0.006). Discussion: The prevalence of dementia related to HIV in our study was similar to the Brazilian and International data. Early diagnosis and treatment are fundamental for preventing HAND development, especially in older patients.

Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity.

Highly active antiretroviral therapy (HAART) is an accepted treatment option for patients with virus infection. Mounting evidence indicated that persistent HAART treatment is implicated with increased morbidity of HIV-associated neurocognitive disorders (HAND) in patients. Tenofovir disoproxil fumarate (TDF), a novel nucleotide reverse transcriptase inhibitor (NRTI), was used in patients with HIV co-infected with HBV. And it is still a vital first-line antiretroviral compounds in HAART. However, whether persistent treatment with TDF is involved in HAND development remains to be further elucidated.In this study, we aimed to discuss the neurotoxicity of TDF. We used SH-SY5Y cells and primary neuronal cells to evaluate the neurotoxicity of TDF in vitro. The cytotoxicity of TDF on SH-SY5Y cells and primary neuronal cells was evaluated by the cell viability and LDH levels by MTT assay and LDH kit, respectively. Hoechst 33342 staining, TUNEL assay and flow cytometry were performed to evaluate the cells apoptosis. The intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production were measured by commercial kits. In addition, the activation level of caspase-3 was evaluated using spectrophotometry and western blotting. Our results showed that TDF treatment significantly induced cell viability and induced apoptosis of SH-SY5Y cells and primary neuronal cells. Furthermore, the ROS levels and MDA productions were significantly up-regulated in nerve cells treated with TDF. CONCLUSION: Our findings indicated that TDF may induce neuronal cell apoptosis through increasing the intracellular ROS and the expression level of caspase-3, which may be related to the increasing prevalence of HAND.

Colorectal Surgery and the acquired immune deficiency syndrome (AIDS)

The impact of the Human Immunodeficiency Virus (HIV) infection in colorectal surgical practice include the undoubted risk of surgeon’s exposure, the atypical conditions that may be encountered and the outcome and long-term benefit of the surgical treatment on the background of the fact that Highly Active Antiretroviral Therapy (HAART)- compliant patients are living longer, but a progression of AIDS in the HAART-naïve patients.

HIV-1 Disease Progression and Drug Resistance Mutations among Children on First-Line Antiretroviral Therapy in Ethiopia.

Background: High rates of disease progression and HIV drug resistance (HIVDR) among adults taking highly active antiretroviral treatment (HAART) in Sub-Saharan Africa were previously documented. However, children were generally not considered despite their greater risk. Hence, this study was aimed to evaluate HIV-1 disease progression and drug resistance mutation among children on first-line antiretroviral therapy in Ethiopia. Method: A longitudinal study was conducted among 551 HIV-positive children (<15 years old) recruited between 2017 and 2019 at 40 antiretroviral treatment delivery sites in Ethiopia. Disease progression was retrospectively measured over a 12-year (2007-2019) follow-up as the progress towards immunosuppression. Two consecutive viral load (VL) tests were conducted in 6-month intervals to assess virologic failure (VF). For children with VF, HIV-1 genotyping and sequencing was performed for the pol gene region using in-house assay validated at the Chinese Center for Disease Control and Prevention, and the Stanford HIVDB v9.0 algorithm was used for identification of drug resistance mutations. The Kaplan-Meier analysis and Cox proportional hazards regression model were used to estimate the rate and predictors of disease progression, respectively. Results: The disease progression rate was 6.3 per 100 person-years-observation (95% CI = 4.21-8.53). Overall immunosuppression (CD4 count < 200 cells/mm3) during the 12-year follow-up was 11.3% (95% CI = 7.5-15.1). Immunosuppression was significantly increased as of the mean duration of 10.5 (95% CI = 10.1-10.8) years (38.2%) to 67.8% at 12 years (p < 0.001). Overall, 14.5% had resistance to at least one drug, and 6.2% had multi-drug resistance. A resistance of 67.8% was observed among children with VF. Resistance to non-nucleotide reverse transcriptase inhibitors (NNRTI) and nucleotide reverse transcriptase inhibitors (NRTI) drugs were 11.4% and 10.1%, respectively. Mutations responsible for NRTI resistance were M184V (30.1%), K65R (12.1%), and D67N (5.6%). Moreover, NNRTI-associated mutations were K103N (14.8%), Y181C (11.8%), and G190A (7.7%). Children who had a history of opportunistic infection [AHR (95% CI) = 3.4 (1.8-6.2)], vitamin D < 20 ng/mL [AHR (95% CI) = 4.5 (2.1-9.9)], drug resistance [AHR (95% CI) = 2.2 (1.4-3.6)], and VF [AHR (95% CI) = 2.82 (1.21, 3.53)] had a higher hazard of disease progression; whereas, being orphan [AOR (95% CI) = 1.8 (1.2-3.1)], history of drug substitution [(AOR (95% CI) = 4.8 (2.1-6.5), hemoglobin < 12 mg/dL [AOR (95% CI) = 1.2 (1.1-2.1)] had higher odds of developing drug resistance. Conclusions: Immunosuppression was increasing over time and drug resistance was also substantially high. Enhancing routine monitoring of viral load and HIVDR and providing a vitamin-D supplement during clinical management could help improve the immunologic outcome. Limiting HAART substitution is also crucial for children taking HAART in Ethiopia.

E66 Arthropathy as the initial presentation of HIV

Abstract Background Human immunodeficiency virus (HIV) has been associated with musculoskeletal disorders which has been estimated to occur in 11–72% of infected patients. Most of these reports however have been in adults with few published cases of HIV associated arthritis in children. The articular manifestations of HIV, especially overt arthritis, can occur at any stage of the disease but are more prevalent in advanced immunosuppression. With the increased access to early diagnosis and highly active antiretroviral therapy (HAART), such complications have increasingly become rare. However, HIV diagnosis may often be missed or delayed in slow progressors, and in such circumstances, these patients may manifest with arthritis as the initial manifestation of HIV. Therefore, there’s need for consideration of HIV associated arthritis in children presenting with arthropathy of undetermined cause. We hereby present a case of arthritis as the initial manifestation of HIV in a child with missed diagnosis of HIV. Methodology/case presentation A 12-year-old boy was admitted in the Kenyatta National Hospital (KNH) paediatric ward with a history of joint pain and swelling for three months. He had otherwise previously been well. He had no history of fever, trauma, preceding gastroenteritis or urine tract infection. He had no chorea, no erythematous rash and no cardiac complications of rheumatic fever. He was not wasted, and was able to walk with great difficulty. He had bilateral knee and right ankle swelling. The swollen joints were warm to touch with positive ballotment and fluid sweep test. Joint aspiration revealed straw coloured joint effusion. Investigations included a positive HIV rapid test with CD4% of 6, CRP 8.33 mg/l (n = &amp;lt;5), Elevated ESR (111 mm in first h) and negative ANA. Bilateral Knee -rays did not reveal any destructive or erosive changes. A diagnosis of HIV arthropathy was made and the patient was started on HAART, HCQ, prednisone and ibuprofen. He improved, with resolution of the joint swellings, was discharged home after 10 days and follow up in the rheumatology and comprehensive care clinics advised. Conclusion HIV arthropathy should be considered in patients manifesting with arthritis of unknown origin; and the patients evaluated for HIV as a strategy for identifying and including them in care. Highly active antiretroviral therapy, steroids, hydroxychloroquine and NSAIDS may be effective therapy for HIV arthropathy. Disclosure statement: The authors have no conflict of interest to declare.

A Case Control Study to Assess Factors Associated with HIV Mother to Child Transmission in Kenya

Background: With the proposal that people with undetectable serum viral loads of HIV cannot transmit, there is a large gap, either due to viral discordance or transcytosis, that would be explaining the persistent 4 to 7 percent vertical transmission of HIV to infants by Kenyan mothers. Therefore, we looked for factors that predispose mothers with HIV to transmit the disease to their children so that policy can be generated for their screening to be conducted if they fit the specified criteria that identifies them as a high-risk group. Methods: Through access to the National Database providing HIV treatment services country wide, we looked for the presence of the available factors from MTCT cases and assessed their association with increased risk of vertical transmission. The factors assessed were mother’s blood plasma viral load (BPVL), geographic location of the mother and child (associated with specific higher and lower socioeconomic status), gender of the baby being born, time age after birth with confirmation of Mother to Child Transmission (MTCT), method of feeding chosen by mothers, age of the mothers, and the regimen of Highly Active Anti Retro Viral treatment (HAART) that the mother and child had been given. Results: Mixed breast feeding posed a much higher risk, mothers of a younger age posed a higher risk, residents of some areas were at higher risks, of note the town of Lamu in Kenya. The at birth stat administration of Niverapin with Zidovudin (NVP+AZT) to the baby was very effective against the transmission, in comparison to any of the other interventions, and having an UD BPVL led to a six-fold reduction the risk of MTCT. Conclusion: There are factors that are associated with a higher risk of vertical transmission from pregnant and lactating UD BPVL mothers which warrant implementation of more stringent policy in their case to achieve Elimination of MTCT(EMTCT) in Kenya. Other factors that were not in the available records and the ones found to have an impact need to be investigated with more accuracy through a prospective study.

Favourable outcomes in RR-TB patients using BPaL and other WHO-recommended second-line anti-TB drugs.

SETTING: According to reports in South Africa, treatment failure rates for rifampicin-resistant TB (RR-TB) are significant and below the WHO target of ≥70%. HIV infection and the use of highly active antiretroviral therapy (HAART) influence how patients receiving anti-TB drugs respond to therapy. In the treatment of RR-TB, more recent medications, including bedaquiline, pretomanid and linezolid (BPaL), have shown promising results.OBJECTIVE: To assess treatment outcomes in RR-TB patients using BPaL and other second-line anti-TB drugs as recommended by the WHO in the South African population.DESIGN: The databases Medline, PubMed, Google Scholar and Embase were searched for studies between 2015 and 2022, which investigated BPaL outcomes in South Africa.RESULTS: Of the 27,259 participants, 21% were on bedaquiline, 1% were taking pretomanid and 9% were taking linezolid as part of their background regimen. About 68% of the patients were HIV-positive, with 59% of them taking HAART.CONCLUSION: Overall, 66% of patients taking BPaL drugs as part of their background regimen had favourable treatment outcomes. Additionally, patients with RR-TB who were HIV-positive and taking HAART while receiving BPaL drugs as part of a background regimen had improved treatment outcomes.