Dolutegravir plus lamivudine versus efavirenz plus tenofovir disoproxil fumarate and lamivudine in antiretroviral-naive adults with HIV-1 infection

Background Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China. Methods This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm. Results Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05). Conclusions DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients. Clinical Trial Registration ChiCTR1900027640 (22/November/2019).

A double-blind, randomized controlled trial to examine the effect of Moringa oleifera leaf powder supplementation on the immune status and anthropometric parameters of adult HIV patients on antiretroviral therapy in a resource-limited setting

Background People living with HIV (PLHIV) in resource-limited settings are vulnerable to malnutrition. Nutritional interventions aimed at improving food insecurity and malnutrition, together with antiretroviral therapy (ART), could improve treatment outcomes. In Nigeria, there is a high awareness of the nutraceutical benefits of Moringa oleifera. Thus, this study aimed to evaluate the effects of Moringa oleifera leaf supplementation on the CD4 counts, viral load and anthropometric of HIV-positive adults on ART. Methods This was a double-blind, randomized study. Two hundred HIV-positive patients were randomly allocated to either the Moringa Oleifera group (MOG) given Moringa oleifera leaf powder or the control group (COG) given a placebo. Changes in anthropometric parameters [weight; body mass index (BMI)] and CD4 cell counts were measured monthly for six months, while HIV-1 viral loads were measured at baseline and the end of the study for both groups. Results Over the study period, the treatment by time interaction shows a significant difference in CD4 counts by treatment group (p<0.0001). A further estimate of fixed effects showed that the CD4 counts among MOG were 10.33 folds greater than COG over the study period. However, the viral load (p = 0.9558) and all the anthropometric parameters (weight; p = 0.5556 and BMI; p = 0.5145) between the two groups were not significantly different over time. All tests were conducted at 95CI. Conclusion This study revealed that Moringa oleifera leaf supplementation was associated with increased CD4 cell counts of PLHIV on ART in a resource-limited setting. Programs in low-resource settings, such as Nigeria, should consider nutritional supplementation as part of a comprehensive approach to ensure optimal treatment outcomes in PLHIV.

Gradual increasing dyslipidemia in treatment-naive male patients with human immunodeficiency virus and treated with tenofovir plus lamivudine plus efavirenz for 3 years

Introduction Since the development of antiretroviral therapy (ART) with TDF plus 3TC plus EFV, this specific regimen has not been studied enough with long-term lipid and uric acid monitoring. Methods A prospective follow-up cohort study was performed. Sixty-one treatment-naive male patients with human immunodeficiency virus (HIV) were divided into three groups based on their baseline CD4+ cell count (26, 12, and 23 patients in the < 200, 200 to 350, and > 350 groups, respectively). The lipid and purine metabolism parameters of the patients over 144 weeks were analyzed. Result Within 144 weeks, TG, LDL-c, TC and HDL-c gradually increased, especially TC and HDL-c (P = 0.001, 0.000, respectively). Moreover, the percentages of hyper-cholesterolemia, hyper LDL cholesterolemia, hyper-triglyceridemia and low HDL cholesterolemia also gradually increased, especially low HDL cholesterolemia significantly increased (P = 0.0007). The lower the baseline CD4+ cell counts were, the higher the TG levels and the lower the TC, LDL-c and HDL-c levels were. But there was significant difference of only baseline LDL-c levels between the three groups (P = 0.0457). No significant difference of the UA level and the percentages of hyperuricemia was found between the different follow-up time point groups or between the three CD4+ cell counts groups (all P > 0.05). The risk factors for dyslipidemia included age, anthropometric parameters and follow-up weeks, and for hyperuricemia was virus load. Conclusions Gradual increasing dyslipidemia was found in male patients with human immunodeficiency virus primarily treated with tenofovir plus lamivudine plus efavirenz for 3 years. There-fore lipid metabolism parameters should be closely monitored during long-term ART with the TDF plus 3TC plus EFV regimen.

The correlation of tuberculosis smear results and immuno-suppression with CD4+ counts as a surrogate marker among HIV infected patients.

Background: Human immunodeficiency virus (HIV) and M.tuberculosis are two intracellular pathogens that interact at the cellular, clinical and population levels. Since the recognition of AIDS in 1981, the number of reported cases of TB in the has increased substantially, especially in regions with high incidence of AIDS. The main aim of this study was to establish weather there is a relationship between sputum smear positives and low CD4 cell counts among HIV infected patients.Materials and methods: This was a retrospective study involving 473 participants. The patients recruited in this study were those who tested HIV positive and smear positive for TB. Their HIV status was determined by performing an HIV blood test, if they were HIV positive their CD4 cell count were then made.Results: This study examined the relation between smear positivity and low CD4 (below 200cells/µl) together with CD8 and CD3 markers as a measure of immune function among patients infected with HIV. The study participants’ constituted males 67% and females 33%. The overall mean age was 33.2 (SD 6.9) with the youngest and oldest participants being 18 and 60 respectively. It was found that smear positive results negatively (r=-0.13; p=0.021) correlated with CD4+ below 200 cells/µl. No correlation was observed between smear positives and CD8+ or CD3+ since the calculated correlation coefficient was not significant 0.007 (p=0.9) and 0.03 (p=0.6) respectively. There are more 3+ smear results below 200 cells/µl than the others while above 200 cells/µl 1+ was the most commonly reported smear result. The scanty smear positives were the least commonly reported result in the low and high CD4 counts. Conclusion: The smear positive result negatively correlated with a low CD4+ (r=-0.13; p=0.021) but no correlation with low CD+8 and CD+3 results was observed. The long held theory that low bacillary counts in patients with low CD4+ counts needs to be revisited. The reduction of CD4+ cell count parallels' that of the total lymphocyte count and is more marked in patients with high bacillary counts. Further, studies are required to confirm these findings

Cd4 T-Lynphocyte count associated with patient infected with Typei &Typeii HIV attending Malali clinic and maternity, Kaduna Kaduna - Nigeria

Background: More than 25 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 2.5 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed [5, 6]. Methods and Findings: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a minimized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology [10]. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity [1,4]

HIV Infection and the Risk of World Health Organization–Defined Sudden Cardiac Death

Background People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear. Methods and Results This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)–defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow‐up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04–1.25), adjusting for possible confounders. In analyses with time‐varying CD4 and HIV viral load, people living with HIV with CD4 counts <200 cells/mm 3 (HR, 1.57; 95% CI, 1.28–1.92) or viral load >500 copies/mL (HR, 1.70; 95% CI, 1.46–1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts >500 cells/mm 3 (HR, 1.03; 95% CI, 0.90–1.18) or HIV viral load <500 copies/mL (HR, 0.97; 95% CI, 0.87–1.09) were not at increased SCD risk. Conclusions HIV infection is associated with increased risk of WHO‐defined SCD among those with elevated HIV viral load or low CD4 cell counts.

Markov modelling of viral load adjusting for CD4 orthogonal variable and multivariate conditional autoregressive mapping of the HIV immunological outcomes among ART patients in Zimbabwe

Background This study aimed to jointly model HIV disease progression patterns based on viral load (VL) among adult ART patients adjusting for the time-varying “incremental transients states” variable, and the CD4 cell counts orthogonal variable in a single 5-stage time-homogenous multistate Markov model. We further jointly mapped the relative risks of HIV disease progression outcomes (detectable VL (VL ≥ 50copies/uL) and immune deterioration (CD4 < 350cells/uL) at the last observed visit) conditional not to have died or become loss to follow-up (LTFU). Methods Secondary data analysis of individual-level patients on ART was performed. Adjusted transition intensities, hazard ratios (HR) and regression coefficients were estimated from the joint multistate model of VL and CD4 cell counts. The mortality and LTFU transition rates defined the extent of patients’ retention in care. Joint mapping of HIV disease progression outcomes after ART initiation was done using the Bayesian intrinsic Multivariate Conditional Autoregressive prior model. Results The viral rebound from the undetectable state was 1.78times more likely compared to viral suppression among patients with VL ranging from 50-1000copies/uL. Patients with CD4 cell counts lower than expected had a higher risk of viral increase above 1000copies/uL and death if their VL was above 1000copies/uL (state 2 to 3 (λ23): HR = 1.83 and (λ34): HR = 1.42 respectively). Regarding the time-varying effects of CD4 cell counts on the VL transition rates, as the VL increased, (λ12 and λ23) the transition rates increased with a decrease in the CD4 cell counts over time. Regardless of the individual’s VL, the transition rates to become LTFU decreased with a decrease in CD4 cell counts. We observed a strong shared geographical pattern of 66% spatial correlation between the relative risks of detectable VL and immune deterioration after ART initiation, mainly in Matabeleland North. Conclusion With high rates of viral rebound, interventions which encourage ART adherence and continual educational support on the barriers to ART uptake are crucial to achieve and sustain viral suppression to undetectable levels. Area-specific interventions which focus on early ART screening through self-testing, behavioural change campaigns and social support strategies should be strengthened in heavily burdened regions to sustain the undetectable VL. Sustaining undetectable VL lowers HIV transmission in the general population and this is a step towards achieving zero HIV incidences by 2030.

Disseminated disease due to non-tuberculous mycobacteria in HIV positive patients: A retrospective case control study

Introduction Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency. Materials and methods In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined. Results Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001). Conclusion In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge.

Virologic Outcomes among People Living with HIV with High Pre-Therapy Viral Load Burden Initiating on Common Core Agents

Background People living with HIV (PLWH) initiating antiretroviral therapy (ART) with viral loads (VL) ≥100,000 copies/mL are less likely to achieve virologic success, but few studies have characterized real-world treatment outcomes. Methods ART-naïve PLWH with VLs ≥100,000 copies/mL initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL) or darunavir (DRV) between 12Aug2013 and 31July2017 were identified from the OPERA Database. Virologic failure was defined as (i) 2 consecutive VLs ≥200 copies/mL after 36 weeks of ART, or (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks, or (iii) 2 consecutive VL ≥200 copies/mL after suppression (≤50 copies/mL) before 36 weeks, or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Cox modelling estimated the association between regimen and virologic failure. Results There were 2,038 ART-naïve patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%) or RAL (2%). Median follow-up was 18.1 months (IQR:12.4-28.9). EVG and DTG initiators were similar at baseline but RAL initiators were older and more likely to be female with low CD4 cell counts while DRV initiators differed notably on factors associated with treatment failure. Virologic failure was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio (95% CI) was 1.46 (1.05, 2.03) for EVG, 2.24 (1.50, 3.34) for DRV, and 4.13 (1.85, 9.24) for RAL. Conclusion ART-naïve PLWH with high VLs initiating on DTG were significantly less likely to experience virologic failure compared to EVG, RAL and DRV initiators.