Antiretroviral-naive Patients Research Articles

Risk Factors Associated with Osteopenia/Osteoporosis in Antiretroviral Therapy Naive HIV Patients

Different ART (antiretroviral therapy) options may affect the risk of osteopenia/osteoporosis in people living with HIV (PLWH) having increased life expectancy. Current guidelines recommend bone mineral density (BMD) measurement only in patients at risk. In our study, we investigated the prevalence of osteopenia/osteoporosis and associated risk factors in naive patients not receiving ART. This study included 116 newly diagnosed, ART naive HIV-positive patients who were studied retrospectively. Vitamin D level, BMD measurement, CD4 and CD8 count, CD4/CD8 ratio, HIV RNA level, body mass index and other risk parameters of ART naive patients were included in our study. Of 116 patients, 103 were male and 13 female. 47.4% (osteoporosis in 4.3%, osteopenia in 43.1%) of patients had osteopenia/osteoporosis. The patients with osteopenia/osteoporosis had older age (39.2±11.0 vs 32.0±8.6, p=0.0001), lower vitamin D levels (16.0±5.0 vs 24.4±6.3, p=0.0001), lower BMI (body mass index) (23.0±4.0 vs 24.6±4.6 p<0.05), lower CD4 and CD8 counts (405.1±885.0 vs 467.3± 695.1; 849.9570.4 vs 1012.0±629.4 respectively, p<0.05). 41.8% had CD4 count ≤200/μL (vs 18.0%, p=0.005). No statistically significant differences were observed in terms of gender distribution, smoking, alcohol and drug use, comorbidities and, additional drug use and HIV RNA >100 000 copies/ml. In multivariate analysis, age and vitamin D level were significant and independent (p<0.05) risk factors with osteoporosis/osteopenia. Being over 40 years of age, CD4 count ≤200/μL, vitamin D level <20 ng/mL and low BMI are the most important risk factors for osteopenia/osteoporosis in ART naive patients. Among these parameters, age and vitamin D level were significant and independent risk factors. These factors may guide the determination of the need for dual-energy x-ray absorptiometry (DXA) testing in ART naive patients and drug choices in the treatment plan.

Genetic landscape for majority and minority HIV-1 drug resistance mutations in antiretroviral therapy naive patients in Accra, Ghana

BackgroundThe successful detection of drug-resistance mutations (DRMs) in HIV-1 infected patients has improved the management of HIV infection. Next-generation sequencing (NGS) to detect low-frequency mutations is predicted to be useful for efficiently testing minority drug resistance mutations, which could contribute to virological failure. This study employed Sanger sequencing and NGS to detect and compare minority and majority drug resistance mutations in HIV-1 strains in treatment-naive patients from Ghana. MethodFrom a previous study, 20 antiretroviral therapy (ART)-naive participants were selected for a cross-sectional study. Sanger sequencing and NGS techniques were used to detect the majority and minority HIV drug resistance (HIVDR) mutations, respectively, in the protease (PR) and partial reverse transcriptase (RT) genes. NGS detected mutations at 1 % and 5 % frequencies and Sanger sequencing at ≥20 % frequencies. The sequences obtained from NGS and Sanger sequencing platforms were submitted to the Stanford HIV drug resistance database for subtyping, mutation identification, and interpretations. ResultsSequences from the twenty participants where the CRF02_AG was the predominant strain (16, 80 %) were analyzed. NGS detected 25 mutations in the RT and PR genes, compared to 21 mutations by Sanger sequencing. Minority DRMs were detected at the prevalence of 55.0 % with NGS against 35 % DRMs by Sanger sequencing. One of the patients had eight different HIVDR variants, with two minority variants. These mutations were directed against PI (K20I and D30DN), NNRTI (Y181C, M23LM and V108I) and NRTI (K65R, M184I, and D67N). ConclusionThe study affirms the usefulness of genomic sequencing for drug resistance testing in HIV. It further shows that Sanger sequencing alone may not be adequate to detect mutations and that NGS capacity should be developed and deployed in the Ghanaian clinical settings for patients living with HIV.

Open Label, Single Centre Study of Babao Relief Capsule as an Adjuvant to HAART in Antiretroviral Naive HIV Patients

HIV continues to be a major global public health issue, having claimed 36.3 million [27.2–47.8 million] lives so far (WHO, 2021). Sub-Sahara Africa remains the far worst affected region, with 20.6 million [16.8 million– 24.4 million] people living with HIV at the end of 2010, compared to 24.4 (22.5-27.3 million) in 2020. Complementary and alternative therapy (CAM) has been used to treat HIV patients by clinicians in conventional health services in combination with highly active antiretroviral therapy (HAART). To determine efficacy of Babao relief capsule when used as an adjuvant to standard HAART in antiretroviral naïve HIV patients. The product is a biological Chinese medicinal preparation, made of herbs. Ingredients include ginseng, beer antler, musk, bezoar, fleeceflower, Chinese angelica, lyceum, pericarpium citri reticulatae, safflower and ophiopogn japonicus. Open Label Phase 1 bridging Clinical trial to study the efficacy of Babao relief capsule when used in combination standard HAART in antiretroviral naïve HIV patients. A total of one hundred and ninety-six (196) adult patients attending the HIV clinic were randomly selected. The interventional group was on Babao relief capsule and HAART while the control group was on HAART only. The study shows general efficacy of the standard HAART drugs. However, the interventional arm showed a significant increase in the CD4 cell count, showing that BRC had booster effects in the efficacy of HAART. Keywords: HIV, Complementary and alternative therapy, Babao relief capsule, standard highly active antiretroviral therapy.

Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India.

Although many drug regimens have been used in the treatment of human immunodeficiency virus (HIV) infection, the National AIDS Control Organization (NACO) of India recommends the use of a fixed-dose combination of tenofovir/lamivudine/dolutegravir (TLD) as a first-line regimen since 2020. In spite of much global data on the use of this combination, experience in the Indian population is still limited. We aim to find out the efficacy and tolerability of this novel regimen, in a tertiary care center of Eastern India. A descriptive observational study, longitudinal in design performed in the antiretroviral therapy (ART) center of a tertiary care hospital in Kolkata, West Bengal, India. All patients who attended the ART center from April 2021 to October 2022 were enrolled in the study following inclusion and exclusion criteria. A detailed history, clinical examination, necessary biochemical tests, and CD4 count of all patients were done at baseline. Subsequently, they were followed up for 6 months with monthly visits when they were enquired about any adverse effects requiring therapy interruptions. At the end of 6 months, CD4 count and viral load were measured. Out of a total sample of 249 patients, the TLD regimen was efficacious in 99.2% (n = 247) in whom viral load was suppressed to <1,000 copies/mL after 6 months of treatment. The regimen had to be temporarily discontinued in 6% of patients (n = 15). The most common cause of treatment interruption was hepatic dysfunction (3.2%) followed by cutaneous manifestation (2.4%). In 14 out of 15 patients, the regimen could be reintroduced and was safely tolerated afterward. Only one patient had to be shifted to an alternative regimen due to tenofovir-induced nephrotoxicity. Thus TLD was tolerated in 99.6% (n = 248) patients. The fixed-dose combination of TLD is a highly efficacious and well-tolerated first-line regimen for ART naïve patients with HIV infection having >95% adherence. How to cite this article: Sengupta D, Ghosh S, Pain S, et al. Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India. J Assoc Physicians India 2023;71(9):72-74.

Durability of single tablet regimen for patients with HIV infection in Southern Taiwan: data from a real-world setting

BackgroundA single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real-world settings. Our aim was to investigate the durability of different initial STR regimens in antiretroviral-naive patients starting STR in southern Taiwan.MethodThis was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure. Secondary endpoints were STR discontinuation due to toxicity/intolerance. Durability was defined as time from the initiation until discontinuation/modification. Kaplan- Meier curves were plotted assessing time to virological suppression, treatment failure and discontinuation for the three STRs and Cox proportional hazards model was used to analyze the factors associated with time to viral suppression, treatment failure or discontinuation.ResultsTwo hundred and twenty-three patients were included: The median follow-up duration (IQR) was 73.9 (48–101.6) weeks, 25 patients (11%) experienced virological failure; the 48 weeks probability of treatment failure was 22.9% (16/70) for Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF), 24.1% (13/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) and 24.2% (24/99) for Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC) (p=0.16). Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to EFV/FTC/TDF, treatment with FTC/RPV/TDF (aHR 8.39, CI 1.98–35.58, p = 0.004) and ABC/DTG/3TC (aHR 8.40, CI 2.39–29.54, p=0.001) were more likely to have treatment failure. The predictors for treatment failure included age ≦ 30 years old (aHR 3.73, CI 1.25–11.17, p = 0.018), switch between different STR (aHR 2.3, CI 1.18–4.50, p = 0.001) and free of active syphilis infection (aHR 0.24, CI 0.08–0.73, p = 0.012). The risk factor for treatment discontinuation included younger age ≦ 30 years old (aHR 3.82, CI 1.21–12.37, p = 0.023), treatment with EFV/FTC/TDF (aHR 8.65, CI 2.64–28.39, p < 0.001) and free of active syphilis infection (aHR 0.16, CI 0.04–0.62, p = 0.006).ConclusionYounger age was associated with treatment failure and drug discontinuation. Active syphilis infection s/p treatment was associated with free from treatment failure and discontinuation. This probably driven by the more frequently sexual health education and counseling when patients had syphilis infection. Treatment with ABC/DTG/3TC was associated with higher risk of treatment failure. The STR durability was dependent on the drug toxicity/intolerance, age and syphilis infection.

Cytokine profiles in highly active antiretroviral treatment non-adherent, adherent and naive HIV-1 infected patients in Western Kenya.

Cytokines play an important role in signaling the immune system to build an adequate immune response against HIV. HIV distorts the balance between pro and anti-inflammatory cytokines causing viral replication. Highly active antiretroviral treatment (HAART) acts by trying to restore pro and anti-inflammatory cytokine balance. It is not clear how HAART non-adherence influences circulating cytokine levels. This study therefore determined cytokine levels in HAART non-adherent individuals. This cross-sectional study recruited 163 participants (51 controls, 23 HIV-1+ HAART naive, 28 HAART-adherent 6 months, 19 HAART-adherent 12 months and 42 HAART non-adherent). Cytokines were analyzed by ELISA while CD4 T cells determined in 3.0 µl of whole blood using BD FACSCaliburTM and viral load in 0.2ml plasma sample using Abbott Molecular m2000sp sample preparation and m2000rt real-time amplification and detection systems (Abbott Molecular Inc., Illinois, USA) according to the manufacturer's methods. IL-4, IL-6, IL-10, TNF-α and TGF-β were significantly elevated in HIV-1 HAART non-adherent compared with HIV-1 HAART adherent and healthy controls P<0.01. IFN- γ was significantly decreased in HIV-1 HAART non-adherent compared with HIV-1 HAART adherent and healthy controls P<0.01. TNF-α and TGF-β were significantly reduced in HIV-1 HAART adherent patients at 12 months compared to those at 6 months P<0.01. IL-4 and IL-10 correlated positively with viral load. IL-4, IL-6, IL-10, TNF-α and TGF- β associated inversely with CD4 T cell counts and body mass index (BMI). This study established that HAART adherence is immunologically beneficial to the pro and anti-inflammatory cytokine balance milieu while non-adherence appears to cause alterations in pro and anti-inflammatory cytokines warping the balance in this dichotomy.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naive Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57).

BackgroundDarunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking.MethodsAdult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL) ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin).ResultsBetween September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/μL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, −2.4%; 95% confidence interval [CI], −11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, −2%; 95% CI, −8.1 to 3.5). There were no differences in CD4 cell count or weight changes.ConclusionsWe could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.

Change in profile of cutaneous manifestations of HIV after the advent of antiretroviral therapy: a retrospective analysis

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;To date, there has been no study conducted in Zambia to determine the prevalence of mucocutaneous conditions among HIV positive patients on antiretroviral therapy.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The aim of the study was to determine the differences in cutaneous manifestations of HIV between HIV positive adult patients on antiretroviral therapy and antiretroviral naïve patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 143 adult HIV/AIDS patients with dermatological manifestations, and fulfilling inclusion criteria, were included. Among the 58 patients on antiretroviral therapy, the most common dermatoses were hyper-pigmentation (18.97%), fungal dermatitis (17.24%) genital herpes (8.62%), papular pruritic eruption (8.62%), oral candidiasis (8.62%) and Kaposi’s sarcoma (6.9%). The most common dermatoses among the 85 antiretroviral naive patients were oral candidiasis (34.12%), herpes Zoster (17.65%), hyper pigmentation (8.24%), eosinophillic folliculitis (7.06%), abscesses (5.88%), herpes labialis (4.71%) and Kaposi's sarcoma (4.71%). Among patients in Stage III of HIV infection, the proportion of patients with infectious dermatoses was significantly greater than the proportion of patients with non-infectious dermatoses (47.5% versus 28.6%; p=0.036).The odds of having an infectious dermatosis were 28% lower for patients on antiretroviral therapy as compared to antiretroviral naive patients (p=0.001).&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;There is a changing profile of muco-cutaneous conditions in HIV infected patients. Infectious dermatoses such as oral candidiasis and Herpes Zoster infections occur more frequently in antiretroviral naïve patients, as compared to patients on ART. Prevention of infectious dermatological conditions occurs with the use of ART.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naïve Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57)

Background: We performed the first head-to-head randomized comparison between D/C/F/TAF and DTG/ABC/3TC in antiretroviral-naive patients. Both treatments were administered as single-tablet regimens. Methods: Adult (>18 y) HIV-infected antiretroviral-naive patients (HLA B5701– and HBV-negative), with VL ≥500 c/mL, were centrally randomized after stratifying by viral load and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 (ITT exposed [ITTe], snapshot analysis), with a non-inferiority margin of 10%. Results: Of 316 subjects randomly assigned to treatment, 306 patients were included in the ITTe analysis (151 and 155) Of these, 94% were male, median age was 35 years, and 79% were men who have sex with men, viral load was 64,848 c/mL, CD4 408/µL, , weight 73 kg, and BMI 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) vs 82% (DTG/3TC/ABC) had VL <50 c/mL (difference –2.4%, 95%CI –11.3 to 6.6). Virologic failure rates were 8% vs 4%, drugs were discontinued due to adverse events in 4% vs 6%, and 8% were lost to follow-up in each arm. In the per protocol analysis, 94% vs 96% patients had VL <50 c/mL (difference –2%, 95%CI –8.1 to 3.5). Three sensitivity ITT analyses were concordant with the primary endpoint. No differences were found in CD4 count increase (+226 vs +260/µL, p=0.1), weight increase (3.0 vs 2.9 kg, p=0.8), or BMI (1.0 vs 0.96 kg/m2, p=0.8) at week 48. The dolutegravir regimen had a more favourable lipid profile and darunavir was associated with lower creatinine (p=0.004) and glucose (p=0.021) increases. No RAMs emerged in any study participant. Conclusions: D/C/F/TAF administered as a single-tablet regimen did not prove to be non-inferior to DTG/ABC/3TC in the ITTe or in the ITT sensitivity analyses. Both regimens were well tolerated, with a similar increase in CD4 counts, weight, and BMI. D/C/F/TAF is an efficacious and well-tolerated alternative to INSTI regimens in antiretroviral-naive patients. Clinical Trial Registration Details: EudraCT Number: 2018-001645-14. Funding Information: Spanish AIDS Research (RIS). Declaration of Interests: DP has received research grants from Gilead, MSD, and ViiV and honoraria for advisory boards and/or conferences from Gilead, MSD, ViiV, and Janssen. SM taken part in speaking activities and has received grants for research from Gilead, Janssen Cilag, Merck Sharp&Dohme, and ViiV Healthcare. JT has received financial compensation for lectures, consultancies, and educational activities, as well as research funding for from Gilead Sciences, Janssen-Cilag, MSD, and ViiV Healthcare. JP has received honoraria for advisories and/or conferences from Gilead, MSD, ViiV and Janssen. JML has received honoraria for advisories and/or conferences from Gilead, ViiV, Theratechnologies and Janssen. ER reports personal fees from MSD, personal fees from Gilead, personal fees from Janssen, personal fees from ViiV Healthcare, outside the submitted work. LM reports having received consulting fees from, Abbvie and Janssen Cilag and has received lecture fees from Abbvie, Janssen Cilag, ViiV and Gilead. MM has received honoraria for advisories and/or conferences from ViiV, Janssen and MSD. AR has received grants for research, educational and advisory activities, from Gilead Sciences, ViiV Healthcare, Janssen Cilag, Abbvie and Merck Sharp&Dohm. FF has received research grants from Gilead and honoraria for advisories and/or conferences from Gilead, MSD, Viiv and Jansen. AP has received honoraria for advisories and/or conferences from Gilead, ViiV and Janssen Cilag. VE has received honoraria for advisory boards and/or conferences from ViiV Healthcare, Janssen, Gilead, MSD Y Thera tech. HK has received financial compensation for consulting work and conferences from Gilead Sciences, Janssen, Merck Sharp Dome and ViiV Healthcare. JTG has been involved in speaking activities from Gilead, Janssen Cilag, and Merck Sharp&Dohme. JM has received honoraria for advisory boards and/or conferences from Gilead, Bristol-Myers Squibb Merck Sharp&Dohme. JS has received financial compensation for consulting work and conferences from Gilead Sciences, Janssen, Merck Sharp Dome and ViiV Healthcare. EM reports grants and personal fees from MSD, grants and personal fees from ViiV Healthcare, personal fees from Gilead, and personal fees from Janssen, outside the submitted work. SM has been involved in speaking activities and has received grants for research from Gilead, Janssen Cilag, Merck Sharp&Dohme, and ViiV Healthcare. RM, PD, CG, AI, AC, DV, MM, AN-A, AC, GF. EB and MPE have no conflict of interests to declare. Ethics Approval Statement: This trial was performed in accordance with the Declaration of Helsinki and approved by the local ethics committees and the Spanish Agency for Medicines and Medical Devices. All participants gave their written informed consent.

Dynamic of HIV-1 Strains Isolated from Newly Diagnosed Antiretroviral Drug Naive Turkish Patients

Dynamic of HIV-1 Strains Isolated from Newly Diagnosed Antiretroviral Drug Naive Turkish Patients

Renal Phosphate Handling in Antiretroviral-naive HIV-Infected Patients.

Human immunodeficiency virus (HIV) infection impairs renal function, thereby affecting renal phosphate metabolism. We prospectively estimated the prevalence of phosphate abnormalities (mild, moderate to life-threatening hypophosphataemia, and hyperphosphataemia) before initiating antiretroviral therapy (ART). A cross-sectional analysis was performed on 170 consecutive newly diagnosed ARTnaive, HIV-infected patients attending our HIV/AIDS clinics over a period of one year. Fifty (50) screened HIV-negative blood donors were used for comparison (controls). Blood and urine were collected simultaneously for phosphate and creatinine assay to estimate fractional phosphate excretion (FEPi %) and glomerular filtration rate (eGFR). eGFR showed significant difference between patients' and controls' medians (47.89ml/ min/1.73m2 versus 60ml/min/1.73m2, p <0.001); which denotes a moderate chronic kidney disease in the patients. Of the 170 patients, 78 (45.9%) had normal plasma phosphate (0.6-1.4 mmol/L); 85 (50%) had hyperphosphataemia. Grades 1, 2 and 3 hypophosphataemia was observed in 3 (1.8%), 3 (1.8%), and 1(0.5%) patient(s) respectively. None had grade 4 hypophosphataemia. Overall, the patients had significantly higher median of plasma phosphate than the controls, 1.4 mmol/L (IQR: 1.0 - 2.2) versus 1.1 mmol/L (IQR: 0.3 - 1.6), p <0.001, implying hyperphosphataemia in the patients; significantly lower median urine phosphate than the controls, 1.5 mmol/L (IQR: 0.7 -2.1) versus 8.4 mmol/L (IQR: 3.4 - 16), p <0.001), justifying the hyperphosphataemia is from phosphate retention; but a non-significantly lower median FEPi% than the controls, 0.96% (IQR: 0.3 -2.2) versus 1.4% (IQR: 1.2 -1.6), p > 0.05. Predictors of FEPi% were age (Odds ratio, OR 0.9, p = 0.009); weight (OR 2.0, p < 0.001); CD4+ cells count predicted urine phosphate among males (p = 0.029). HIV infection likely induces renal insufficiency with reduced renal phosphate clearance. Thus, hyperphosphataemia is highly prevalent, and there is mild to moderate hypophosphataemia but its life-threatening form (grade 4) is rare among ART-naive HIV patients.

The Pattern of Haematological Changes in the Baseline Blood Cell Counts and the CD4&amp;amp;#8314; T Lymphocyte Levels among Antiretroviral Therapy Na&amp;#239;ve Adult HIV Positive Patients in a Nigerian Hospital

Background: Haematological abnormalities are strong independent predictors of morbidity and mortality in HIV infection. Objectives of the Study: This study was carried out to assess the pattern of the changes in the baseline peripheral blood cell counts among adult HIV positive patients. To also determine the CD4+ T cell levels and its correlation with the changes in the baseline cell counts of the patients using HIV negative blood donors as controls. Methods: This was a case controlled prospective study. The subjects were antiretroviral therapy naive adult HIV positive patients and HIV negative blood donor controls. Five milliliters (5 mls) of venous blood was collected from the cubitus of every consecutive consenting subject. Blood sample was analysed for baseline complete blood cell counts and the CD4+ T lymphocyte levels using Sysmex and Cyflow R Counter autoanalysers respectively. Obtained data was analysed with the statistical package for the social scientist (SPSS version 20.0). The Erythrocyte sedimentation rate of subjects was measured by the manual standard Westergreen method. Results: Of 300 subjects, there were 139 (46.3%) males and 161 (53.7%) females in the study. Anaemia was found in 72 (29.2%), leucopenia in 20 (8%) and thrombocytopenia in 6 (2.4%) of the patients. The mean erythrocyte sedimentation rates of the subjects were 81.88 mm/hr and 9.46 mm/hr (p = 0.000) for the patients and the controls respectively. The mean CD4+ T lymphocyte cell counts were 293 cells/μl and 750 cells/μl (p = 0.000) for the patients and controls respectively. Conclusion: Anaemia, leucopenia and thrombocytopenia were more prevalent among the studied HIV positive patients.

Is immune recovery different depending on the use of integrase strand transfer inhibitor-, non-nucleoside reverse transcriptase- or boosted protease inhibitor-based regimens in antiretroviral-naive HIV-infected patients?

To analyse whether integrase inhibitor (InSTI)-based regimens achieve better immunological recovery than NNRTI- or boosted PI (bPI)-based regimens as initial ART. In a retrospective analysis, we selected patients who initiated ART with two NRTIs plus an InSTI, an NNRTI or a bPI and maintained both the same 'third drug' and an HIV-RNA <50 copies/mL in ≥95% of determinations once undetectable viral load had been achieved. We compared CD4+ count, %CD4+ and CD4+/CD8+ ratio recovery over 2 years. Data were analysed using mixed-effects regression models for repeated measures. Of the 836 patients included, 208, 481 and 147 initiated with InSTI, NNRTI and bPI, respectively. For CD4+, %CD4+ and CD4+/CD8+ two main slopes were identified: from month 0 to month 6, with the highest increments; and from month 6 to month 24, with smaller increases every semester. Although the patients on InSTI achieved undetectable viral load faster, for CD4+ and %CD4+ there were no differences in the slopes of change according to the third drug either for the first phase (P=0.137 and P=0.393, respectively) or from month 6 onwards (P=0.834 and P=0.159, respectively). The increase in CD4+/CD8+ was slightly higher for bPI compared with InSTI (difference of 0.0119, 95% CI 0.0020-0.0205; P=0.018), but clinically negligible. From month 6 onwards, no differences were found between treatment groups (P=0.176). Immune restoration measured as CD4+ count, %CD4+ and CD4+/CD8+ increases was independent of the third antiretroviral drug class used when given with two NRTIs.

Lessons learned: Retrospective assessment of outcomes and management of patients with advanced HIV disease in a semi-urban polyclinic in Epworth, Zimbabwe.

IntroductionHIV continues to be one of the leading causes of infectious death worldwide and presentation with advanced HIV disease is associated with increased morbidity and mortality. Recommendations for the management of advanced HIV disease include prompt screening and treatment of opportunistic infections, rapid initiation of ART and intensified adherence support. We present treatment outcomes of a cohort of patients presenting with advanced HIV disease in a semi-urban Zimbabwean polyclinic.MethodsRetrospective cohort analysis of adult patients enrolled for care at Epworth polyclinic, Zimbabwe between 2007 and end June 2016. Treatment outcomes at 6 and 12 months were recorded. Multivariate logistical regression analysis was undertaken to identify risk factors for presentation with advanced HIV Disease (CD4 count less than 200 cells/mm3 or WHO stage 3 or 4) and risks for attrition at 12 months.Results16,007 anti-retroviral therapy naive adult patients were included in the final analysis, 47.4% of whom presented with advanced HIV disease. Patients presenting with advanced HIV disease had a higher mortality rate at 12 months following enrollment compared to early stage patients (5.11% vs 0.45%). Introduction of a package of differentiated care for patients with a CD4 count of less than 100 cells/mm3 resulted in diagnosis of cryptococcal antigenaemia in 7% of patients and a significant increase in the diagnosis of TB, although there was no significant difference in attrition at 6 or 12 months for these patients compared to those enrolled prior to the introduction of the differentiated care.ConclusionsThe burden of advanced HIV disease remained high over the study period in this semi-urban polyclinic in Zimbabwe. Introduction of a package of differentiated care for those with advanced HIV disease increased the diagnosis of opportunistic infections and represents a model of care which can be replicated in other polyclinics in the resource constrained Zimbabwean context.

HIV-1 Transmitted Drug Resistance Mutations in Recently Diagnosed Antiretroviral-Naive Patients in Belém, Pará, Northern Brazil

HIV-1 Transmitted Drug Resistance Mutations in Recently Diagnosed Antiretroviral-Naive Patients in Belém, Pará, Northern Brazil

Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.

Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients. A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1. In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%. Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85). No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus. The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor. Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05). The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses. Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B. These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.

Rare occurrence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients.

Doravirine is a novel HIV-1 NNRTI recently shown to be non-inferior to both darunavir/ritonavir and efavirenz in combination therapy with two NRTIs in treatment-naive patients. Doravirine has an in vitro resistance profile that is distinct from other NNRTIs and retains activity against viruses containing the most frequently transmitted NNRTI mutations. The aim of this study was to examine the prevalence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients in Europe. From 2010 to 2016, 9764 treatment-naive patients were tested for NNRTI antiretroviral drug resistance by bulk sequencing in Greece, Italy and France. We studied the prevalence of doravirine resistance-associated mutations previously identified in vitro: V106A/M, V108I, Y188L, V190S, H221Y, F227C/L/V, M230I/L, L234I, P236L, Y318F and K103N/Y181C. Among 9764 sequences, 53.0% and 47.0% of patients had B and non-B subtypes, respectively. Overall, the presence of at least one doravirine resistance-associated mutation (n = 137; 1.4%) or the K103N/Y181C mutations (n = 5; 0.05%) was very rare. The most prevalent mutations were V108I (n = 62; 0.6%), Y188L (n = 18; 0.2%), H221Y (n = 18; 0.2%) and Y318F (n = 23; 0.2%). The frequency of doravirine resistance-associated mutations was similar between B and non-B subtypes. In comparison, the prevalence of rilpivirine, etravirine, nevirapine and efavirenz resistance was higher whatever algorithm was used (ANRS: 8.5%, 8.1%, 8.3% and 3.9%, respectively; Stanford: 9.9%, 10.0%, 7.5% and 9.4%, respectively). The prevalence of doravirine resistance-associated mutations is very low in antiretroviral-naive patients. These results are very reassuring for doravirine use in naive patients.

Association Between Health-Related Quality of Life and Physical Functioning in Antiretroviral-Naive HIV-Infected Patients.

Background:Poor functional status can significantly affect Health-Related Quality of Life (HRQoL) of HIV patients. However, there is scarce information on the functional profile of such patients before starting antiretroviral therapy (ART).Objective:To estimate the association between health-related quality of life and physical functioning in Antiretroviral-Naive HIV-infected patients.Methods:We conducted a cross-sectional study with HIV-infected patients older than 18 years, and naïve to antiretroviral therapy. The patients were evaluated for functional profile by pulmonary function (forced vital capacity, forced expiratory volume at one second, and Tiffeneau index), handgrip strength, and six-minute walk test in a cross-sectional study. HRQoL was evaluated by the 36-Item Short-Form Health Survey and its Physical (PCS) and Mental (MCS) Component Summaries. Multiple linear regression analyses were used to evaluate the association of predictor variables with PCS and MCS scores.Results:We found lower HRQoL among females patients, with far below average impairment of mental health component. Both male and female patients presented lower 6MWD function test values. Patients with dynapenia were older than patients without it, presented lower PCS mean score, lower family income, poor 6 MWD function test, lower FVC, and lower FEV1 t. Multivariable logistic regression analyses showed that Grip Strength, age and family income were predictor variables for Physical component of HRQoL. Female gender and smoking habit were predictive for the mental component of HRQoL.Conclusion:HRQoL in HIV, drug-naïve patients is predicted by level of dynapenia, smoking, income and gender. Therefore, lifestyle changes and active exercising can help to improve HRQoL in such patients.

Levels of pro-inflammatory biomarkers among HIV patients on highly active antiretroviral therapy (HAART) and HAART naive patients

Inflammation is the immune response of the body to infection and injury. Inflammation aims at eliminating the pathogen or causative agent, removing necrotic cells and tissues and initiating repair process. IL-6. TNF-α and CRP are biomarkers of inflammation. This study sought to determine the pro-inflammatory markers among HIV patients on HAART and HAART naive patients. This was a hospital-based, case control study conducted among 150 participants. HIV patients’ on HAART (n = 50) and HAART naive HIV (n = 50) patients and the control group (n = 50) was HIV Seronegative individuals. Venous blood was drawn from each of the participant. Serial dilutions of standards of TNF-α, IL-6 and CRP were made and mixed with 10 μL of patients’ blood. Absorbance was read at 450 nm within 15 min with Mindray MR-96A reader. Among the study population, IL-6 levels was higher in HAART naive HIV patients 17.66(13.00 - 24.10) ng/L, and these same group also recorded the highest CRP and TNF-α levels of 1453(328.8 – 2510) µg/L and 318.3(123.0 - 497.9) ng/L respectively. The present study revealed elevated levels of pro-inflammatory cytokines (IL-6, CRP and TNF-α) in seropositive HIV groups compared to seronegative group.

Levels of pro-inflammatory biomarkers among HIV patients on highly active antiretroviral therapy (HAART) and HAART naive patients

Levels of pro-inflammatory biomarkers among HIV patients on highly active antiretroviral therapy (HAART) and HAART naive patients