Immunodeficiency at antiretroviral therapy start: five-Year adult data (2012-2017) based on evolving national policies in rural mozambique

Before the 2015 implementation of "Test and Start," the initiation of combination antiretroviral therapy (ART) was guided by specific CD4 cell count thresholds. As scale-up efforts progress, the prevalence of advanced HIV disease at ART initiation is expected to decline. We analyzed the temporal trends in the median CD4 cell counts among adults initiating ART and described factors associated with initiating ART with severe immunodeficiency in Zambézia Province, Mozambique. We included all HIV-positive, treatment-naive adults (age ≥ 15 years) who initiated ART at a Friends in Global Health (FGH)-supported health facility between September 2012 and September 2017. Quantile regression and multivariable logistic regression models were applied to ascertain the median change in CD4 cell count and odds of initiating ART with severe immunodeficiency, respectively. A total of 68,332 patients were included in the analyses. The median change in CD4 cell count under "Test and Start" was higher at +68 cells/mm3 (95% CI: 57.5-78.4) compared with older policies. Younger age and female sex (particularly those pregnant/lactating) were associated with higher median CD4 cell counts at ART initiation. Male sex, advanced age, WHO Stage 4 disease, and referrals to the health facility through inpatient provider-initiated testing and counseling (PITC) were associated with higher odds of initiating ART with severe immunodeficiency. Although there were reassuring trends in increasing median CD4 cell counts with ART initiation, ongoing efforts are needed that target universal HIV testing to ensure the early initiation of ART in men and older patients.

Clinical outcomes of first-line antiretroviral therapy in Latin America: analysis from the LATINA retrospective cohort study.

Nearly 2 million people are infected with human immunodeficiency virus (HIV) in Latin America. However, information regarding population-scale outcomes from a regional perspective is scarce. We aimed to describe the baseline characteristics and therapeutic outcomes of newly-treated individuals with HIV infection in Latin America. A Retrospective cohort study was undertaken. The primary explanatory variable was combination antiretroviral therapy based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The main outcome was defined as the composite of all-cause mortality and the occurrence of an AIDS-defining clinical event or a serious non-AIDS-defining event during the first year of therapy. The secondary outcomes included the time to a change in treatment strategy. All analyses were performed according to the intention to treat principle. A total of 937 treatment-naive patients from four participating countries were included (228 patients with PI therapy and 709 with NNRTI-based treatment). At the time of treatment initiation, the patients had a mean age of 37 (SD: 10) years and a median CD4 + T-cell count of 133 cells/mm(3) (interquartile range: 47.5-216.0). Patients receiving PI-based regimens had a significantly lower CD4 + count, a higher AIDS prevalence at baseline and a shorter time from HIV diagnosis until the initiation of treatment. There was no difference in the hazard ratio for the primary outcome between groups. The only covariates associated with the latter were CD4 + cell count at baseline, study site and age. The estimated hazard ratio for the time to a change in treatment (NNRTI vs PI) was 0.61 (95% CI 0.47-0.80, p < 0.01). This study concluded that patients living with HIV in Latin America present with similar clinical outcomes regardless of the choice of initial therapy. Patients treated with PIs are more likely to require a treatment change during the first year of follow up.

Multiple facets of HIV-associated renal disease

HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count ≥200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 ≥200 cells/mm3 had eGFR >60 mL·min-1·(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count ≥200 cells/mm3 was associated with better renal function after 2 years of follow-up.

Evaluation of late presentation for HIV treatment in a reference center in Belo Horizonte, Southeastern Brazil, from 2008 to 2010

Introduction: Since 1996 Brazil has provided universal access to free antiretroviral therapy, and as a consequence, HIV/AIDS patients' survival rate has improved dramatically. However, according to scientific reports, a significant number of patients are still late presenting for HIV treatment, which leads to consequences both for the individual and society. Clinical and immunological characteristics of HIV patients newly diagnosed were accessed and factors associated with late presentation for treatment were evaluated. Methods: A cross-sectional study was carried out in an HIV/AIDS reference center in Belo Horizonte, Minas Gerais, in Southeastern Brazil from 2008 to 2010. Operationally, patients with late presentation (LP) for treatment were those whose first CD4 cell count was less than 350 cells/mm3 or presented an AIDS defining opportunistic infection. Patients with late presentation with advanced disease (LPAD) were those whose first CD4 cell count was less than 200 cells/mm3 or presented an AIDS defining opportunistic infection. LP and LPAD associated risk factors were evaluated using logistic regression methods. Results: Five hundred and twenty patients were included in the analysis. The median CD4 cell count was 336 cells/mm3 (IQR: 130-531). Two hundred and seventy-nine patients (53.7%) were classified as LP and 193 (37.1%) as LPAD. On average, 75% of the patients presented with a viral load (VL) >10,000 copies/ml. In multivariate logistic regression analysis the factors associated with LP and LPAD were age, being symptomatic at first visit and VL. Race was a factor associated with LP but not with LPAD. Conclusion: The proportion of patients who were late attending a clinic for HIV treatment is still high, and effective strategies to improve early HIV detection with a special focus on the vulnerable population are urgently needed. .

Evaluation of late presentation for HIV treatment in a reference center in Belo Horizonte, Southeastern Brazil, from 2008 to 2010.

INTRODUCTION: Since 1996 Brazil has provided universal access to free antiretroviral therapy, and as a consequence, HIV/AIDS patients' survival rate has improved dramatically. However, according to scientific reports, a significant number of patients are still late presenting for HIV treatment, which leads to consequences both for the individual and society. Clinical and immunological characteristics of HIV patients newly diagnosed were accessed and factors associated with late presentation for treatment were evaluated. METHODS: A cross-sectional study was carried out in an HIV/AIDS reference center in Belo Horizonte, Minas Gerais, in Southeastern Brazil from 2008 to 2010. Operationally, patients with late presentation (LP) for treatment were those whose first CD4 cell count was less than 350 cells/mm(3) or presented an AIDS defining opportunistic infection. Patients with late presentation with advanced disease (LPAD) were those whose first CD4 cell count was less than 200 cells/mm(3) or presented an AIDS defining opportunistic infection. LP and LPAD associated risk factors were evaluated using logistic regression methods. RESULTS: Five hundred and twenty patients were included in the analysis. The median CD4 cell count was 336 cells/mm(3) (IQR: 130-531). Two hundred and seventy-nine patients (53.7%) were classified as LP and 193 (37.1%) as LPAD. On average, 75% of the patients presented with a viral load (VL) >10,000 copies/ml. In multivariate logistic regression analysis the factors associated with LP and LPAD were age, being symptomatic at first visit and VL. Race was a factor associated with LP but not with LPAD. CONCLUSION: The proportion of patients who were late attending a clinic for HIV treatment is still high, and effective strategies to improve early HIV detection with a special focus on the vulnerable population are urgently needed.

Alcohol dependence and CD4 cell count: is there a relationship?

Alcohol and other drugs use seem to be common among people infected with HIV on antiretroviral treatment (ART). Their effects on HIV progression is still in debate. This study aimed to assess the association between alcohol and drug use and an HIV disease progression biomarker (CD4 cell count) among patients on ART. A cross-sectional study was carried out at an HIV treatment center affiliated with Medical School of the University of São Paulo, Brazil. Four hundred and thirty-eight HIV-positive patients on ART were interviewed by trained psychiatrists and psychologists using the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Alcohol Use Disorders Identification Test (AUDIT), 17-item Hamilton Rating Scale for Depression, and the Simplified Medication Adherence Questionnaire (SMAQ). In the previous month, 219 (50%) and 41 (9.3%) patients reported use of alcohol and illicit drugs, respectively. Fifty patients (12.6%) were classified as having harmful alcohol use by AUDIT. According to SCID-I, 80 patients (18.3%) were alcohol abusers, 24 (5.5%) alcohol dependents, and 21 (4.2%) had a current depressive disorder. Almost 73% (n = 319-72.8%) of the patients were adherent to ART. Alcohol dependents were nine times (p < 0.01) more likely to have CD4 cell count ≤200/mm(3), and this association was independent of ART adherence. In conclusion, alcohol dependence seems to be associated with low CD4 cell count in HIV-positive patients. Based on these data, HIV health care workers should always assess alcohol consumption in the treatment setting, and patients should be advised that alcohol dependence may be linked to low CD4.

Determinants of immunological and virological responses to antiretroviral therapy amongst HIV-infected adults in central Argentina: negative influence of hepatitis C infection.

BACKGROUND: The purpose of this study was to update the epidemiological data on the prevalence of coinfection with hepatitis C virus (HCV) and HIV, and to identify whether specific clinical and epidemiological factors influenced the response of HIV-positive adults to highly active antiretroviral therapy (HAART). METHODS: This retrospective observational cohort study of 238 HIV-infected patients evaluated the effect of different epidemiological and clinical parameters (including HCV coinfection) on therapy response among HIV-infected adults initiating HAART. Multiple logistic regression models were used to identify factors associated with therapy response and estimated risk coefficients. RESULTS: Seroprevalence of HCV infection in this population was 26% (62/238). We did not observe a significant association between immunological or virological response relating to patient gender or HAART regimen. However, this analysis showed that HCV serological status, age at HIV diagnosis, duration of treatment and WHO clinical stage of AIDS (<200 CD4 cells/ml independently of viral load either < or > to 100,000 copies/ml), were significantly associated with immunological and virological responses to HAART. CONCLUSIONS: These results show further evidence that hepatitis C serostatus is associated with a reduced response to HAART.

Impacto de la inmunodepresión basal y su grado de recuperación al año de terapia antirretroviral en sobrevida, complicaciones oportunistas y reacción de recuperación inmune / Impact of baseline CD4 count, immune recoveny and viral suppression at 7 year of first highly active antiretroviral therapy on survival, AIDS defining events and immune recovery reactions

Background: Baseline (BL) CD4 cell count is a major factor in outcome of highly active antiretroviral therapy (HAART); treatment induced immune recovery and viral response can modulate this outcome. Aim: To evaluate the association between baseline CD4 cell count and outcome during the first HAART régimen. Material and methods: Prospective study in 2,050 patients on first HAART with a follow up (f/u) ofat least 1 year. All had BL CD4 and viral load (VL) counts which were repeated at least twice a year. Patients were grouped according to BL CD4 (cells/mm³) in <100 (Gl), 100-199 (G2) and ≥ (G3). Groups were further divided according to immune and vírologícal response at 1 year in CD4 > or < 200 and VL detectable or undetectable (<80 copies/mL). Outcome measures were death, ALUS defining events (ADE) and, as a surrogate marker of immune recovery reaction, herpes zoster (HZ). Resulte: During the first year of follow up, 113 patients (10.8 percent) diedin Gl (n =1,044), 17 (2.5 percent) in G2 (n =675) (Gl-2 p <0.05) and 9 (2.7 percent) in G3 (n =331) (G2-3 p NS). One hundred twenty five of919 (13.6 percent) patients alive at 1 year had ADE in Gl, 55/643 (8.5 percent) in G2 (p <0.05) and 20/320 (5.2 percent) in G3 (G2-3 p NS). ADEs with follow up CD4 >vs< 200 were: 25/274 (9.1 percent) vs 100/643 (15 7 percent) in Gl (p <0.005); 28/404 (6.9 percent) vs 27/235 (11.2 percent) in G2 (p NS) and 18/281 (6.4 percent) vs 2/41 (4.8 percent) in G3 respectively (p NS). Detectable VL was an additional risk for ADE only in Gl without CD4 recovery. HZ was seen in 6.6 percent of Gl vs 4 percent in G2 (p <0.05) and 4.3 percent in G3. HZ rate was higher in all groups reaching a follow up CD4 >200 than those who did not, with a statistically significant difference at p <0.05 only in Gl (9.5 percent vs 5.3 percent). Conclusions: The occurrence of death and ADE during the first year of HAART was significantly higher in patients with aBL CD4...