Higher CD4 Counts Research Articles

Integrase Strand Transfer Inhibitors Play the Main Role in Greater Weight Gain Among Men With Acute and Early HIV Infection.

BackgroundThe predictors of weight gain remain unclear in people with acute and early HIV infection (AEH).MethodsEligible antiretroviral-naïve men diagnosed with AEH from January 1, 2000, to December 31, 2019, were enrolled in an observational cohort study at the University California, San Diego. The study used multivariable mixed-effect linear regression models to analyze differences in the rate of weight gain over time between participants receiving early vs deferred antiretroviral therapy (ART) treatment, low vs high baseline CD4 count and HIV RNA, and different classes of ART.ResultsA total of 463 participants were identified, with mean CD4 cell count of 507 cells/μL and log HIV RNA of 5.0 copies/mL at study entry. There was no difference in the rate of weight gain between participants who did and did not receive ART within 96 weeks of incident HIV infection. Neither a baseline CD4 count of <350 cells/μL nor a baseline HIV RNA of >100 000 copies/mL was a predictor of weight gain. Compared with persons taking non-nucleoside reverse transcriptase inhibitor–based regimens, those who received integrase strand transfer inhibitor (INSTI)–based regimens showed greater weight gain over time.ConclusionsNeither baseline CD4 count and HIV RNA nor early ART was associated with weight change in the first 96 weeks following incident HIV infection. Use of INSTI-based regimens represented a major driver of weight gain in men who initiated ART with relatively higher CD4 cell counts.

Lymphnode cytopathology and CD4 count in HIV positive patients

Introduction: CD4 is an important prognostic as well as therapeutic marker in the management of HIV and this study identifies the correlation between CD4 counts and FNAC lymphnode (LN) patterns in these patients. Study Design: The study was conducted in the rural areas at Nalgonda district by Kamineni Institute of Medical Sciences, Telangana. Eventhough Fine Needle Aspiration Cytology (FNAC) was done on total 56 selected patients who had lymphadenopathy and were tested HIV positive, only 50 of them have CD4 counts and were selected as final study group. Suspected cytosmears have acid fast staining done by Ziehl Nelson technique. The final cytopathological findings were correlated with CD4 counts. Results: In our study, high CD4 counts were associated with reactive lymphadenitis (26%;13/50) most and Low CD4 counts were associated with less frequent suppurative lymphadenitis and particulary TB lymphadenitis was noticed in 56% (28/50) and morphologically exhibited 4 different patterns– caseous with epitheloid granuloma, only caseous necrosis, only epitheloid granuloma and suppurative. Conclusion: CD4 count correlated well with the different stages of immunosuppression in HIV patients. The patients with reactive lymphadenitis demonstrated high CD4 counts suggesting good immunological response. The low CD4 counts seen in patients with suppurative lymphadenitis and cryptococcal infection suggests severe immuno-compromised state. Keywords: Cytopathology, CD4 count, Granuloma, HIV, Lymphnode, Tuberculosis.

Dynamics of HIV-1 Molecular Networks Reveal Effective Control of Large Transmission Clusters in an Area Affected by an Epidemic of Multiple HIV Subtypes.

This study reconstructed molecular networks of human immunodeficiency virus (HIV) transmission history in an area affected by an epidemic of multiple HIV-1 subtypes and assessed the efficacy of strengthened early antiretroviral therapy (ART) and regular interventions in preventing HIV spread. We collected demographic and clinical data of 2221 treatment-naïve HIV-1–infected patients in a long-term cohort in Shenyang, Northeast China, between 2008 and 2016. HIV pol gene sequencing was performed and molecular networks of CRF01_AE, CRF07_BC, and subtype B were inferred using HIV-TRACE with separate optimized genetic distance threshold. We identified 168 clusters containing ≥ 2 cases among CRF01_AE-, CRF07_BC-, and subtype B-infected cases, including 13 large clusters (≥ 10 cases). Individuals in large clusters were characterized by younger age, homosexual behavior, more recent infection, higher CD4 counts, and delayed/no ART (P < 0.001). The dynamics of large clusters were estimated by proportional detection rate (PDR), cluster growth predictor, and effective reproductive number (Re). Most large clusters showed decreased or stable during the study period, indicating that expansion was slowing. The proportion of newly diagnosed cases in large clusters declined from 30 to 8% between 2008 and 2016, coinciding with an increase in early ART within 6 months after diagnosis from 24 to 79%, supporting the effectiveness of strengthened early ART and continuous regular interventions. In conclusion, molecular network analyses can thus be useful for evaluating the efficacy of interventions in epidemics with a complex HIV profile.

Elevated interleukin levels are associated with higher severity and mortality in COVID 19 – A systematic review, meta-analysis, and meta-regression

Background and aimsCOVID 19 pneumonia commonly leads to ARDS. The occurrence of ARDS in COVID 19 patients is thought to occur secondary to an exaggerated immunologic response. In this meta-analysis, we aim to comprehensively study the various levels of immunological parameters in patients with COVID 19. Materials and methodsWe performed a systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and medRxiv with the search terms, “COVID-19” and “Interleukin”. The outcome of interest was prognosis in COVID 19 patients. ResultsWe performed meta analysis of 16 studies. Higher counts of CD4 and CD8 with Lower Levels of TNF-a, IL2R, IL6, IL8 were observed on patients with good prognosis compared to patients with poor prognosis; −0.57 (pg/mL) (−1.10, −0.04, p = 0.04), (I2 91%, p < 0.001); −579.84 (U/mL) (−930.11, −229.57, p < 0.001), (I2 96%, p < 0.001); −1.49 (pg/mL) (−1.97, −1.01, p < 0.001), (I2 94%, p < 0.001); −0.80 (pg/mL) (−1.21, −0.40, p < 0.001), (I2 79%, p < 0.001); −2.51 (pg/mL) (−3.64, −1.38, p < 0.00001), (I2 98%, p < 0.001) respectively. Meta-regression showed age and hypertension (coefficient: 1.99, and −1.57, p = 0.005, and 0.006) significantly influenced association between IL-6 and poor outcome. ConclusionElevated immune response to coronavirus occurs in COVID 19 patients. Higher counts of CD4 and CD8 were seen in patients with good prognosis compared to patients with poor prognosis, with Lower levels of TNF-a, IL2R, IL6, IL8, were observed in patients with good prognosis compared to patients with poor prognosis.

Prevalence of nonsuppressed viral load and associated factors among HIV-positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population-based nationally representative surveys.

IntroductionThe global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months.MethodsWe analysed data from the population‐based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross‐sectional household surveys. Data collection included structured interviews, home‐based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second‐line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self‐report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second‐line ART.ResultsWe included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non‐disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second‐line ART.ConclusionsCountries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor‐ or integrase inhibitor‐based regimens may further reduce NVL prevalence.

Temporal trends of early mortality and its risk factors in HIV-infected adults initiating antiretroviral therapy in Uganda.

BackgroundA decline in mortality rates during the first 12 months of antiretroviral therapy (ART) has been mainly linked to increased ART initiation at higher CD4 counts and at less advanced World Health Organization (WHO) clinical stages of HIV infection; however, the role of improved patient care has not been well studied. We estimated improvements in early mortality due to improved patient care.MethodsWe conducted a retrospective cohort study of HIV-infected individuals ages 18 and older who initiated ART at the Mengo HIV Counseling and Home Care Clinic between 2006 and 2016. We conducted a mediation analysis using generalized structural equation models with inverse odds ratio weighting to estimate the natural direct and indirect effects of ART initiation time on early mortality.FindingsAmong 6,847 patients, most were female (69%), with a median age of 32 (interquartile range [IQR] = 28–38), versus a median age of 38 (IQR = 32–45) for males. The median CD4 count at ART initiation increased from 142 cells/ul (95% confidence interval [CI] = 135–150) in 2006–2010 to 302 cells/ul (95% CI = 283–323) in 2015–2016 (p < 0·001). The number of patients at WHO clinical stages I/II increased from 52% in 2006–2010 to 78% in 2015–2016 (p < 0·001). Annual early mortality decreased from 8·8 deaths/100 person years (PYS) in 2006 to 2.5 deaths/100 pys in 2016 (p < 0·001). Mediation by CD4 counts and WHO clinical stages accounted for 54% of the total effect of ART initiation timing on early mortality. In comparison, 46% remained as the direct effect, reflecting the contribution of improved patient care.InterpretationImproved patient care practices should be promoted as a strategy for reducing early mortality after ART initiation, above and beyond the effects from ART initiation at higher CD4 counts and less advanced WHO clinical stage alone.FundingThis research was supported by the President's Emergency Plan for AIDS Relief (PEPFAR), the National Institute of Allergy and Infectious Diseases Division of Intramural Research, and the National Cancer Institute.

Predictors of Virological Failure and Time to Viral Suppression of First-Line Integrase Inhibitor-Based Antiretroviral Treatment.

BackgroundIntegrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of persons with human immunodeficiency virus (HIV). We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens.MethodsWe studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations.ResultsWe observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3–3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1–3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3–.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2–.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6–.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0–1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome.ConclusionsFactors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.

Assessment of Markers of Depression and CD4 Cell Count among Adult HIV-Positive Patients on Anti-Retroviral at a Nigerian University Teaching Hospital

Objective: Depression is a common mental health problem among people living with HIV/AIDS (PLWHA); because low count of lymphocytes with cluster of differentiation 4 (CD4 cell count) is associated with severe symptoms of HIV infection, there are thoughts that low CD4 cells count can provoke depressive illness. This study was conducted to determine the relationship between CD4 count and depression among adult HIV positivepatients attending Family Medicine clinics at University of Ilorin Teaching Hospital (UITH), Ilorin, Nigeria.Method: A hospital based descriptive cross-sectional study was done over a period of 6 months among 350 systematically randomly selected adult HIV-positive patients. PHQ-9 was used to obtain information on depression and the CD4 count was determined using a flow-cytometric method. Data were obtained and analyzed using SPSS-17. Chi-square was used to determine degree of association between the depression and the level of CD4 count. P-value of &lt; 0.05 was considered statistically significant.Results: The prevalence of depression among the respondents was 33.4%. The prevalence of depression was highest among respondents with low CD4 count (≤349cells/ul), 37.0%, and least among those with high CD4 count (≥500cells/ul), 28.3%. This relationship was however not statistically significant.Conclusion: The overall prevalence of depression was high among the respondents (33.4%) suggesting the need for routine depression screening among HIV positive patients. There was no statistically significant association between presence of depression and level of CD4 count (p-value=0.302).&#x0D; Keywords: Depression, CD4count, PLWHA, Family Medicine, UITH.

Association of Plasma Soluble Vascular Cell Adhesion Molecule-1 and sCD14 With Mortality in HIV-1-Infected West African Adults With High CD4 Counts.

Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. In this article, we report the association between 11 biomarkers and medium-term mortality in HIV-infected West African adults. In Temprano ANRS 12136, antiretroviral therapy (ART)-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the World Health Organization criteria were met. Participants who completed the 30-month trial follow-up were invited to participate in a posttrial phase. The posttrial phase end point was all-cause death. We used multivariate Cox proportional models to analyze the association between baseline plasma biomarkers [IL-1ra, IL-6, soluble vascular cell adhesion molecule 1 (sVCAM-1), sCD14, D-dimer, fibrinogen, IP-10, sCD163, albumin, high-sensitivity C-reactive protein, and 16S rDNA] and all-cause death in the Temprano participants randomized to defer ART. Four hundred seventy-seven patients (median age 35 years, 78% women, and median CD4 count: 379 cells/mm) were randomly assigned to defer starting ART until the World Health Organization criteria were met. The participants were followed for 2646 person-years (median 5.8 years). In the follow-up, 89% of participants started ART and 30 died. In the multivariate analysis adjusted for the study center, sex, baseline CD4 count, isoniazid preventive therapy, plasma HIV-1 RNA, peripheral blood mononuclear cell HIV-1 DNA, and ART, the risk of death was significantly associated with baseline sVCAM-1 (≥1458 vs. <1458: adjusted hazard ratio 2.57, 95% confidence interval: 1.13 to 5.82) and sCD14 (≥2187 vs. <2187: adjusted hazard ratio 2.79, interquartile range 1.29-6.02) levels. In these sub-Saharan African adults with high CD4 counts, pre-ART plasma sVCAM-1 and sCD14 levels were independently associated with mortality.

S1640 Primary Colonic Lymphoma Manifesting as Colovesical Fistula

INTRODUCTION: Gastrointestinal (GI) tract is the most common extranodal site of Non-Hodkin lymphoma (NHL) and constitutes about 4% of all GI malignancies. The most common sites of involvement in the GI tract are stomach followed by the small intestine. We report a case of primary colonic lymphoma manifesting with colovesical fistula in a patient with human immunodeficiency virus (HIV) infection. CASE DESCRIPTION/METHODS: A 50-year-old male with a history of HIV on antiretroviral therapy with undetectable viral load and a CD4 count of 260 cells/µL, presented with burning micturition, intermittent passage of air and feculent material in urine, on and off for one year. He has chronic nonbloody diarrhea and noticed thirty-pound weight loss over the past three months. At admission, he was afebrile, hypotensive, and had sinus tachycardia (114/min). Physical examination was significant for palpable, tender left lower quadrant mass but no hepatosplenomegaly, bowel distention, or peripheral lymphadenopathy. Laboratory data revealed anemia (HB 8.5 g/dl), leukocytosis (WBC 14000/µl), mildly elevated platelet count (422,000/µl), acute kidney injury (serum creatinine 2.50, baseline 0.81 mg/dL) and normal CEA level. Urine was brown, turbid with microscopy showing RBC and WBC ( >180/hpf). CT scan of abdomen and pelvis with contrast revealed a large circumferential mass measuring 14.5 cm × 10 cm in sigmoid colon with a fistulous communication to the urinary bladder suggestive of colovesical fistula. Colonoscopy confirmed a partially obstructing, large circumferential, ulcerated mass within the proximal sigmoid colon. Pathology was consistent with diffuse large B-cell lymphoma (+BCL2, +MYC). PET-CT scan showed increased FDG uptake in the sigmoid colon along with adrenal gland and bone but no involvement of lymph nodes, liver, or spleen. A diverting colostomy was performed and subsequently, he was started on dose-adjusted R-EPOCH Regimen. The patient received 5 cycles of chemotherapy and a repeat PET-CT scan showed resolution of activity in the sigmoid colon, bone, and adrenal gland. Retroperitoneal ultrasound during chemotherapy showed persistence of colovesical fistula. DISCUSSION: HIV-AIDS predisposes patients to different malignancies including NHL in about 10% of patients. Colonic involvement of primary NHL is exceedingly rare. High viral load and low CD4 counts (< 100) are risk factors for NHL in HIV patients. We describe here an unusual presentation of NHL manifesting as colovesical fistula, in a patient with HIV.Figure 1.: Computed tomographic scan of abdomen & pelvis in sagittal view showing large sigmoid mass (long arrow). Air-fluid level of orally administered contrast noted in the urinary bladder. (short arrow).Figure 2.: Colonoscopy shows a fungating, ulcerating mass in the sigmoid colon, nearly obstructing the lumen.Figure 3.: Initial PET tumor imaging whole body.

S1387 A Case of Rapidly Progressive Disseminated Cytomegalovirus Causing Acute Pancreatitis in the Setting of Acquired Immune Deficiency Syndrome

INTRODUCTION: Widespread dissemination of opportunistic infections is increasingly recognized in AIDS, many times found on autopsy when causing gastrointestinal pathology. However, premortem acute pancreatitis caused by opportunistic infections is rarely diagnosed. CMW is a double stranded DNA with a reported prevalence of 60-100% (1). In an immunocompromised individual, disseminated CMV can cause a variety of pathology. We will discuss a middle aged female who was found to have acute pancreatitis in the setting of CMV viremia causing rapid deterioration. CASE DESCRIPTION/METHODS: 45 year old El Salvadorian female presented with abdominal pain, nausea, vomiting and diarrhea. Lipase on admission was 154 U/L. CT showed evidence of acute pancreatitis, gastritis and colitis. Denied alcohol use and triglyceride levels were normal. An MRCP did not show any obstruction of the bile duct. Patient became febrile and HIV test was positive with high viral load and CD4 count less than 20. Denies being sexually active but was raped while crossing the border two years prior. Course complicated by septic shock requiring intubation and vasopressors secondary to PCP pneumonia. Patient suffered from a GI bleed and EGD brushings showed candida throughout the upper GI tract. Biopsies of the gastric body, antrum and duodenum came back positive for CMV. CMV DNA was >20000 IU/ml and started on Ganciclovir. Repeat CT still showed evidence of acute pancreatitis. Patient went into renal failure requiring CVVH and ultimately the patient passed due to complications of septic shock. DISCUSSION: CMV in immunocompromised patients is common, but CMV pancreatitis is rare. A retrospective study analyzed autopsy CMV in AIDS patients and 81/164 had CMV infection, but organ failure was in 17 patients. Another study conducted autopsies on patients with CMV infections, and 10% were found to pancreatic involvement. The exact mechanism is still not well understood, but one proposed mechanism suggests endothelial cells release trypsin which results in pancreatic inflammation and autodigestion of cellular membranes. In this case, the patient met diagnostic criteria for pancreatitis by sharp epigastric abdominal pain with loss of appetite and CT findings of acute pancreatitis. Lipase levels are not correlated to the severity of disease, however in the three documented cases of CMV pancreatitis lipase was >1000 U/L. CMV should be on differential when a patient with AIDS presents with acute pancreatitis.

Identifying and predicting longitudinal trajectories of care for people newly diagnosed with HIV in South Africa.

BackgroundPredicting long-term care trajectories at the time of HIV diagnosis may allow targeted interventions. Our objective was to uncover distinct CD4-based trajectories and determine baseline demographic, clinical, and contextual factors associated with trajectory membership.MethodsWe used data from the Sizanani trial (NCT01188941), in which adults were enrolled prior to HIV testing in Durban, South Africa from August 2010–January 2013. We ascertained CD4 counts from the National Health Laboratory Service over 5y follow-up. We used group-based statistical modeling to identify groups with similar CD4 count trajectories and Bayesian information criteria to determine distinct CD4 trajectories. We evaluated baseline factors that predict membership in specific trajectories using multinomial logistic regression. We examined calendar year of participant enrollment, age, gender, cohabitation, TB positivity, self-identified barriers to care, and ART initiation within 3 months of diagnosis.Results688 participants had longitudinal data available. Group-based trajectory modeling identified four distinct trajectories: one with consistently low CD4 counts (21%), one with low CD4 counts that increased over time (22%), one with moderate CD4 counts that remained stable (41%), and one with high CD4 counts that increased over time (16%). Those with higher CD4 counts at diagnosis were younger, less likely to have TB, and less likely to identify barriers to care. Those in the least favorable trajectory (consistently low CD4 count) were least likely to start ART within 3 months.ConclusionsOne-fifth of people newly-diagnosed with HIV presented with low CD4 counts that failed to rise over time. Less than 40% were in a trajectory characterized by increasing CD4 counts. Patients in more favorable trajectories were younger, less likely to have TB, and less likely to report barriers to healthcare. Better understanding barriers to early care engagement and ART initiation will be necessary to improve long-term clinical outcomes.

Re-engagement in care of people living with HIV lost to follow-up after initiation of antiretroviral therapy in Mali: Who returns to care?

We assessed cumulative incidence rates of and factors associated with re-engagement in HIV care for PLHIV lost to follow-up in Mali. HIV-1-infected individuals lost to follow-up before 31/12/2013, ≥ 18 years old, who started ART from 2006 to 2012 at one of 16 care centres were considered. Loss to follow-up (LTFU) was defined as an interruption of ≥ 6 months during follow-up. The re-engagement in care in PLHIV lost to follow-up before 31/12/2013 was defined as having at least one clinical visit after LTFU. The cumulative incidence rates of re-engagement in care was estimated by Kaplan-Meier and its predictive factors were assessed using Cox models. Socio-demographic characteristics, clinical and immune status, period, region, centre expertise level, and distance from home at the start of ART plus a combined variable of duration of ART until LTFU and 12-month change in CD4 count were assessed. Multiple imputation was used to deal with missing data. We included 3,650 PLHIV lost to follow-up before December 2013, starting ART in nine outpatient clinics and seven hospitals (5+2 in Bamako and 4+5 in other regions): 35% male, median (IQR) age 35 (29-43), and duration of ART until LTFU 11 months (5-22). Among these PLHIV, 1,975 (54%) were definitively LTFU and 1,675 (46%) subsequently returned to care. The cumulative incidence rates of re-engagement in care rose from 39.0% at one year to 47.0% at three years after LTFU. Predictors of re-engagement in care were starting ART with WHO stage 1-2 and CD4 counts ≥ 200 cells/μL, being treated for ≥ 12 months with CD4 count gain ≥ 50 cells/μL, or being followed in Bamako. People followed at regional hospitals or outpatient clinics ≥ 5 km away, or being treated for ≥ 12 months with CD4 count gain < 50 cells/μL were less likely to return to care. Starting ART with a higher CD4 count, better gain in CD4 count, and being followed either in Bamako or close to home in the regions were associated with re-engagement in care.

Body mass index and noninfectious comorbidity in HIV-positive patients commencing antiretroviral therapy in Zimbabwe.

The aim of the study was to describe the prevalence of elevated body mass index (BMI) in a cohort of treatment-naïve people living with HIV (PLWH) and to investigate the association of BMI with CD4 count and noninfectious comorbidities including hypertension and renal impairment. A retrospective cohort study of 1598 PLWH at the Newlands Clinic in Harare, Zimbabwe was carried out. Data were extracted from the medical records at baseline and 6months after initiation of treatment. The univariate association between BMI and CD4 count was assessed and multiple regression models were used to predict factors associated with loss of renal function and change in CD4 count at 6months. Overweight and obesity (BMI≥25kg/m2 ) were prevalent in this cohort (34%), as was the presence of hypertension (18%). Higher BMI was associated with a higher CD4 count at baseline and 6months (B=0.28 and 0.24, respectively; P<0.001 for both), adjusted for age and sex. The presence of hypertension independently predicted loss of renal function at 6months (B=-15.31; P<0.001), adjusted for BMI, CD4 count and sex. High BMI itself was also independently associated with a decline in renal function (B=-0.41; P=0.003), adjusted for other significant variables. We demonstrate a high prevalence of overweight/obesity and hypertension in an urban cohort of PLWH in Zimbabwe. Higher BMI was associated with a higher CD4 count, both before and 6months after commencing antiretroviral therapy; it was also associated with loss of renal function in this cohort.

Immunovirological treatment outcomes after 2 years of antiretroviral therapy in children living with the human immune deficiency virus in Lagos Nigeria

Background/objective: The World Health Organization (WHO) recommends routine assessment of antiretroviral treatment outcomes to detect treatment failure early and prevent the development of drug resistance. The aim of this study was to describe treatment outcomes of antiretroviral therapy (ART) over 2 years in children living with the human immune deficiency virus enrolled in the paediatric HIV clinic at the Lagos UniversityTeaching Hospital (LUTH).Materials and methods: This was a retrospective study of antiretroviral treatment outcomes in 278 children receiving antiretroviral therapy at the paediatric HIV clinic of LUTH. Demographic, clinical and laboratory data were retrospectively collected from clinical records of pediatric patientswho received antiretroviral therapy for 2 years ( from November 2015 to December 2017) . Virological failure was defined as viral load &gt; 400 copies/ml and immunological failure was defined as a CD4 count &lt;100 cells/mm3 or CD4 % &lt;15% after receiving antiretroviral agents for 12 months. Data was analysed using graph pad prism version 5.0.Results: After 12 months on antiretroviral therapy (ART), 101 (36%) had virological failure while 14 (5%) and 36 (13%) failed immunologically [CD4 count &lt;100 cells/mn3 and CD4 &lt;15% respectively]. Virological blips were observed at 24 months in 6.1% of patients while immunovirological discordance occurred in 30% of patients (poor virological clearance despite good immunological recovery) . High baseline viral load (&gt;5000 copies/ml), poor adherence (&lt;95%) and low baseline CD4 counts (101-249 cells/mn3) were significantly associated with virological failure, while low baseline CD4 counts (&lt;350 cells/mn3) and poor adherence (&lt;95%) were significantly associated with immunologic failure.Conclusion: The treatment outcomes observed in this study are similar to those reported in earlier studies. At 1 and 2 years of antiretroviral therapy , there was immune restoration however 101 (36%) and 87 (31%) respectively had virological failure despite good adherence to therapy and good Immunological restoration. This calls for early initiation and switch to second and third line drugs .&#x0D; Key words: Human immunodeficiency virus (HIV), zidovudine, lamivudine, nevirapine, virological blips, immunovirological discordance , children, Nigeria.

Perceived social support, depression and their impact on quality of life of people living with HIV in India

ABSTRACT Universal access to Antiretroviral Treatment (ART) has transformed HIV/AIDS into a chronic disease and issues like social support and Quality of life (QOL) have emerged as important components of care. Perceived social support influences QOL in People Living with HIV (PLHIV), though this has not been studied well in India. PLHIV were assessed for Social Support using the Multidimensional Scale of Perceived Social Support (MSPSS) and QOL was assessed with the Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire. The factors impacting social support and its effect of on QOL were analysed. Amongst the 109 study subjects, 62 (56.9%) were men, 47 (43.1%) were women, mean age was 35 ± 7.5 years, 85.3% had WHO stage 1 disease and 80 (73.4%) were receiving ART. Only 43.1% subjects perceived high overall social support. Social support (from family/friends/others) was associated positively with physical functioning (p = 0.001), social and cognitive functioning (p = 0.000) and significantly inversely associated with depression (p = 0.002). Higher perceived social support was seen to correlate with higher CD4 count (Peak, Nadir and Current; p < 0.05) and better adherence (p = 0.003). It is concluded that social support, including support from beyond family, have a significant impact on clinical endpoints and QOL in PLHIV.

Survival analysis of people living with human immunodeficiency virus: a study in a teaching hospital

Background: Antiretroviral therapy (ART) have changed the outlook of people living with HIV (PLHIV) by transforming the dreaded infection to a chronically manageable disease. However, there is scant of reports which analyses quantitatively the survival benefit of PLHIV under ART. Objectives of this study were to determine the survival time of adult PLHIV who are on ARV. To analyse the factors determining survival outcome of PLHIV on ARV.Methods: This was an observational study in centre of excellence (COE) ART Centre, RIMS, Imphal from April 2004 to December 2009. Details from the data entered in documents of the ART programme were followed up every 3 months for 60 months from the date of initiation of ARV. All PLHIV above 18 years of age and undergoing antiretroviral therapy were included.Results: Survival rate following initiation of ARV was found to be significantly high among PLHIV. Higher CD4 count at the time of ARV initiation had better prognosis. Mortality was high among IDUs and they had high incidence of co-infections with HCV and HBV. The currently available ARV drugs under NACO programme have better suppression of HIV, are less toxic, low pill burden. The combined regimen used in the earlier days were not much inferior to the current ARV drugs if initiated timely with proper prophylaxis of OIs, good adherence, good nutrition and timely management of toxicities and IRIS.Conclusions: Timely treatment with ARV drugs provided under the national programme with good adherence and regular follow-up improves the survival of PLHIV.

CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies.

A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH. PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations. We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296-552)/mm3, 936 (670-1304)/mm3, and 0.43 (0.28-0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2-37) and 18 (7-42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23-3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58-6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60-6.56] for KS; HR = 5.28 [95% CI = 2.17-12.83] for NHL). Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.

Models of service delivery for optimizing a patient's first six months on antiretroviral therapy for HIV: an applied research agenda.

Differentiated models of service delivery (DSD models) for HIV treatment in sub-Saharan Africa were conceived as a way to manage rapidly expanding populations of experienced patients who are clinically "stable" on antiretroviral therapy (ART). Entry requirements for most models include at least six months on treatment and a suppressed viral load. These models thus systematically exclude newly-initiated patients, who instead experience the conventional model of care, which requires frequent, multiple clinic visits that impose costs on both providers and patients. In this open letter, we argue that the conventional model of care for the first six months on ART is no longer adequate. The highest rates of treatment discontinuation are in the first six-month period after treatment initiation. Newly initiating patients are generally healthier than in the past, with higher CD4 counts, and antiretroviral medications are better tolerated, with fewer side effects and substitutions, making extra clinic visits unnecessary. Improvements in the treatment initiation process, such as same-day initiation, have not been followed by innovations in the early treatment period. Finally, the advent of COVID-19 has made it riskier to require multiple clinic visits. Research to develop differentiated models of care for the first six-month period is needed. Priorities include estimating the minimum number and type of provider interactions and ART education needed, optimizing the timing of a patient's first viral load test, determining when lay providers can replace clinicians, ensuring that patients have sufficient but not burdensome access to support, and identifying ways to establish a habit of lifelong adherence.

HIV Reservoir Decay and CD4 Recovery Associated With High CD8 Counts in Immune Restored Patients on Long-Term ART.

Background: Whether varying CD8 counts influence the human immunodeficiency virus (HIV) reservoir and CD4 restoration in patients with CD4 counts ≥ 500 cells/μL after long-term antiretroviral therapy (ART) remains unknown. In this study, we analyzed relationships between CD8 levels and viral reservoir decay or CD4 recovery in immune restored patients on long-term ART.Methods: Chronic HIV-infected patients who received 5 years of ART with CD4 counts ≥ 500 cells/μL were grouped according to CD8 counts: CD8 <500 (Group 1), 500–1,000 (Group 2), and ≥1,000 cells/μL (Group 3). CD4 recovery, viral decay, CD8 T-cell function, and their correlations were analyzed during ART among the three groups.Results: Dynamics of viral decay and CD4 recovery were different among the three groups. Both viral decay and CD4 recovery were higher in Group 3 than the other two groups after 5 years of ART, mainly during years 3–5 of ART. Higher expression levels of Ki67 while PD-1 levels were lower on CD8 T-cells in Group 3 compared with the other groups, and Group 3 showed stronger CD8 T-cells functional capacity after 3 years of ART. Reduced HIV DNA levels and increased CD4 counts between years 3 and 5 of ART were positively correlated with CD8 counts and function.Conclusions: High CD8 counts are beneficial for persistent viral decay and CD4 recovery in immune restored patients during long-term ART.