Baseline CD4 Lymphocyte Count Research Articles

1276. Noninvasive Assessment of Change in Hepatic Fibrosis Following Initiation of Integrase Inhibitors in Women Living with HIV

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in persons with HIV and can lead to hepatic fibrosis. Integrase strand-transfer inhibitors (INSTIs), first-line agents in antiretroviral therapy (ART), are associated with increased body mass index (BMI), particularly in women living with HIV (WLWH). We evaluated change in hepatic fibrosis risk following INSTI initiation in WLWH. Table 1.Change over time in hepatic fibrosis scores among group switching to INSTI-regimens versus group staying on non-INSTI regimens INSTI=integrase strand-transfer inhibitor; SD=standard deviation; FIB-4=Fibrosis-4 Score (calculated by Age*AST/[platelet count*ALT1/2]; APRI=AST to Platelet Ratio Index (calculated by [AST/AST upper limit of normal]/platelet count); NFS = Non Alcoholic Fatty Liver Disease Fibrosis Score (calculated by -1.675+(0.037*age) + (0.094*body mass index)+(1.13*hyperglycemia or diabetes [yes=1, no=0])+ (0.99*AST/ALT)-(0.013*platelet count)-(0.66*albumin)); CI=Confidence Interval. Linear regression model with unstructured covariance matrix for repeated observations with a person. Adjusted models for all outcomes included the following covariates: age, race/ethnicity, education, baseline CD4 lymphocyte count, baseline antiretroviral anchor drug, and abacavir, tenofovir disoproxil fumarate, and tenofovir alafenamide use. Body mass index was included in models for FIB-4 and APRI only. Age was included for APRI only. Methods Data from 2007-2020 were analyzed from virologically-suppressed WLWH enrolled in the Women’s Interagency HIV Study (WIHS). We excluded WLWH with untreated viral hepatitis, heavy alcohol use and autoimmune or metabolic chronic liver disease. WLWH who switched to or added an INSTI to ART were compared to women who remained on non-INSTI ART. Outcomes included change in noninvasive markers of hepatic fibrosis: Fibrosis-4 (FIB4), AST to Platelet Ratio Index (APRI), and NAFLD fibrosis score (NFS), measured 4-12 months before and 4-19 months post INSTI switch/add. Longitudinal linear regression models compared change over time in each outcome by group, adjusted for covariates. Results 872 WIHS participants (323 INSTI, 549 non-INSTI) were followed for a median 3.0 years (Q1 2.0, Q3 4.5). Mean age was 47.2 years (SD 9.0), 61% were Non-Hispanic Black, and mean BMI was 31.4 (8.8) kg/m2. Absolute mean changes in FIB4, APRI, and NFS scores were +0.021, -0.005, +0.194, respectively, in the INSTI group compared to +0.003, -0.011, +0.016, respectively, in the non-INSTI group (Table 1). No significant differences in mean AST and ALT change between the INSTI and non-INSTI groups were noted. There was a significant increase in NFS score in the INSTI group (p< 0.0001) and this difference remained in adjusted models (p=0.0135). Compared to the non-INSTI group, a larger proportion of participants in the INSTI group changed to a higher NFS risk category: 15.7% vs 9.0%, p=0.014. Conclusion Starting INSTIs was associated with minimal change in FIB4 and APRI scores but increased NFS score in WLWH. The increase in NFS score likely reflects BMI gain with INSTI use, as BMI is not factored into FIB4 or APRI calculators and AST and ALT did not change significantly. Nonetheless, patients starting INSTIs need close monitoring of metabolic changes and low thresholds for additional noninvasive liver fibrosis testing. Disclosures Michael A. Yu, MD, Ligera: Advisor/Consultant Maria L L. Alcaide, MD, Gilead: Advisor/Consultant Adaora A. Adimora, MD, MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support Jennifer C. Price, MD, PhD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support Phyllis C. Tien, MD, MSc, Gilead: Grant/Research Support|Merck: Grant/Research Support Cecile D. Lahiri, MD, MS, Theratechnologies: Advisor/Consultant.

Clinical parameters, selected HLA and chemokine gene variants associated with late presentation into care of people living with HIV/AIDS.

Late presentation into care remains a significant problem in the diagnosis of HIV infection, and may negatively impact the Joint United Nations Program HIV/AIDS elimination targets. Host genetics affects the tempo of HIV disease progression and therefore may influence clinical status at care entry. Longitudinal data were collected for 863 Caucasian patients followed up at Pomeranian Medical University, Szczecin, Poland. Single nucleotide polymorphisms in CCR2 (rs1799864), CX3CR1 (rs3732378), HLAC-35 (rs9264942), CCR5 promoter (rs1799988) as well as 32 base pair CCR5 mutation and HLA-B*5701 genotypes were correlated with the clinical and immunologic patient status at care entry. Late presentation was defined as baseline CD4 lymphocyte count <350 cells/μL or history of AIDS-defining illness, while advanced HIV disease as baseline CD4 lymphocyte count <200 cells/μL or AIDS. Of the analyzed gene variants, the CCR2 (rs1799864) GG genotype was more frequent among patients presenting for care with a CD4 lymphocyte count <200/μL (82.6% for GG homozygotes vs. 74.5% for allele A carriers, p=0.01). The presence of the heterozygous wt/Δ32 genotype at the CCR5 gene was associated with a higher frequency of asymptomatic infection (18.9% for wt/Δ32 heterozygotes vs. 12% for wt/wt homozygotes, p=0.03). As expected, this association was also observed among late presenters compared to patients presenting for care earlier (13.7% vs. 19,7%, respectively, p=0.04). Finally, HLA-B*5701 was less common among late presenters (5%) compared to patients who entered care early (9.6%, p=0.01) or patients with advanced HIV disease (8.9% vs. 5.2%, p=0.02). Late presentation was associated with the GG homozygous genotype at the CCR2 rs1799864 SNP, while both the HLA-B*5701 variant and the CCR5 wt/Δ32 were associated with more favorable clinical profile at care entry.

The association of CD4 lymphocyte count with drug hypersensitivity reaction to highly active antiretroviral therapy, trimethoprim sulfamethoxazole, and antitubercular agents in human immunodeficiency virus patients.

BackgroundThe introduction of highly active antiretroviral therapy (HAART) and antibiotic regimens for the treatment of human immunodeficiency virus (HIV) and its concomitant opportunistic infections, respectively, significantly improve the morbidity and mortality of the infected patients. However, these drugs commonly cause drug hypersensitivity reactions (DHRs) in patients with acquired immunodeficiency syndrome. The reason proposed are multifactorial, which includes immune hyperactivation, changes in drug metabolism, patient cytokine profiles, oxidative stress, genetic predisposition, and the principal target in HIV patients, the CD4+ lymphocytes.ObjectiveThis study determined the association of CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents among HIV patients.MethodsThis is a retrospective analytical study. Review of charts were done. The demographic and clinical profile used a descriptive statistics such as mean and standard deviation for quantitative data and frequency and percent for categorical data. Chi-square and Fisher exact tests were used to measure the degree of the relationship of CD4 count and DHRs.ResultsA total of 337 eligible patients were included. There was a 25% incidence of hypersensitivity reactions. However, the prevalence of DHRs across the different CD4 groups was not statistically significant (p = 0.167). Likewise, the study found no significant association between the CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents (p = 0.311). The most common DHR was morbilliform rash, and nevirapine was the most reported antiretroviral drug causing DHR.ConclusionThere was no association in the CD4 count and DHRs to first-line HAART, trimethoprim sulfamethoxazole, and antitubercular agents. Hence, regardless of the baseline CD4 lymphocyte count, the physician should be vigilant in monitoring hypersensitivity reactions. Patient education on common DHRs is very important upon diagnosis of HIV and/or initiation of treatment.

Interatrial blocks prevalence and risk factors for human immunodeficiency virus-infected persons.

BackgroundInteratrial blocks are considered a new important risk factor for atrial fibrillation and cerebrovascular events. Their prevalence and clinical implications have been reported in general population and several subgroups of patients but no data from HIV-infected populations, with a non-negligible prevalence of atrial fibrillation, has been previously reported.MethodsWe conducted a cross-sectional study in a previously enrolled cohort of randomly selected middle-aged HIV-infected patients who attended our hospital and were clinically stable.Patients underwent both a 12-lead rest electrocardiogram and clinical questionnaires while epidemiological, clinical and HIV-related variables were obtained from electronic medical records and interviews with the patients. Electrocardiograms were then analyzed and codified using a standardized form by two trained members of the research team who were blinded to clinical variables.ResultsWe obtained electrocardiograms from 204 patients with a mean age of 55.22 years, 39 patients (19.12%) presented an interatrial block, 9 (4.41%) advanced and 30 (14.71%) partial. Patients with interatrial block had a lower nadir lymphocyte CD4 count (124 vs 198 cells, p = 0.02) while advanced interatrial blocks were associated to older age (62.16 vs. 54.95 years, p = 0.046) and hypertension (77.8% vs. 32.3%, p = 0.009). We did not find differences regarding baseline CD4 lymphocyte count or CD4/CD8 lymphocyte ratio. Clinical variables and functional capacity among patients with or without interatrial block were similar.ConclusionsIn a cohort of clinically stable HIV infected patients the prevalence of interatrial blocks, specially advanced, is high and associated to previously known factors (age, hypertension) and novel ones (nadir CD4 lymphocyte count).

Factors associated with first-line antiretroviral treatment failure in adult HIV-positive patients: a case-control study from Ethiopia

BackgroundTreatment failure has become a significant challenge in patients taking antiretroviral therapy (ART). The aim of the present study was to identify risk factors for first-line ART failure among patients attending clinical follow-up.MethodsA 1:2 matched case-control study (by age, sex, and treatment duration since initiated on ART) was conducted from June 2015 to July 2017 on adult patients (aged ≥15 years) who were on ART for at least 6 months. Cases were selected from patients who were switched to second-line ART after first-line ART failure (viral load ≥1000 copies/mL). Controls were randomly selected from patients on first-line ART with viral load < 50 copies/mL. Data were collected using an interview questionnaire, reviewing chart and electronic health records and laboratory tests. Multivariate logistic regression analysis was performed to identify risk factors for treatment failure.ResultsOf the 273 patients who participated in this study, 55% were males. Ninety-one cases were compared with 182 controls. The median age of participants was 40 years and the median duration of treatment since initiated on ART was 69 months. Independent risk factors associated with first-line antiretroviral treatment failure were discontinuation of ART (adjusted odds ratio (AOR) = 9.8, 95% confidence interval (CI): 4.0–23.8), baseline CD4 lymphocyte count ≤50 cells/mm3 (AOR = 3.8, 95% CI: 1.5–9.6) and persistent diarrhea (AOR = 4.4, 95% CI: 1.5–13.2). The risk of ART failure was high and comparable whether the duration of ART discontinuation was greater or less than 1 month (crude odds ratio (COR) = 6.3 and 8. 5 respectively, p-value < 0.001). Frequent eating of a diet containing wheat or barley (AOR = 2.3, 95% CI: 0.9–5.4) showed a trend to be a risk factor for first-line ART failure (p-value = 0.064).ConclusionsOur findings underscore the importance of avoiding ART discontinuation of any duration, early initiation of ART and diarrhea management to prevent first-line ART failure.

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV

The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven. To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB. This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016. Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria. The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens. Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log10 copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/μL), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O'Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n = 4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence. Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance. clinicaltrials.gov Identifier: NCT00933790.

Treatment outcomes and their determinants in HIV patients on Anti-retroviral Treatment Program in selected health facilities of Kembata and Hadiya zones, Southern Nations, Nationalities and Peoples Region, Ethiopia.

BackgroundEthiopia has been providing free Antiretroviral Treatment (ART) since 2005 for HIV/AIDS patients. ART improves survival time and quality of life of HIV patients but ART treatment outcomes might be affected by several factors. However, factors affecting treatment outcomes are poorly understood in Ethiopia. Hence, this study assesses treatment outcomes and its determinants for HIV patients on ART in selected health facilities of Kembata and Hadiya zones.MethodsA retrospective cohort study was conducted on 730 adult HIV/AIDS patients who enrolled antiretroviral therapy from 2007 to 2011 in four selected health facilities of Kembata and Hadiya zones of Southern Ethiopia. Study subjects were sampled from the health facilities based on population proportion to size. Data was abstracted using data extraction format from medical records. Kaplan-Meier survival function was used to estimate survival probability. Cox proportional hazards regression model was used to identify factors associated with time to death.ResultMedian age of patients was 32.4 years with Inter Quartile Range (IQR) [15, 65]. The female to male ratio of the study participants’ was 1.4:1. Median CD4 count significantly increased during the last four consecutive years of follow up. A total of 92 (12.6 %) patients died, 106(14.5 %) were lost to follow-up, and 109(15 %) were transferred out. Sixty three (68 %) deaths occurred in the first 6 months of treatment. The median survival time was 25 months with IQR [9, 43]. After adjustment for confounders, WHO clinical stage IV [HR 2.42; 95 % CI, 1.19, 5.86], baseline CD4 lymphocyte counts of 201 cell/mm3 and 350 cell/mm3 [HR 0.20; 95 % CI; 0.09−0.43], poor regimen adherence [HR 2.70 95 % CI: 1.4096, 5.20], baseline hemoglobin level of 10gm/dl and above [HR 0.23; 95 % CI: 0.14, 0.37] and baseline functional status of bedridden [HR 3.40; 95 % CI: 1.61, 7.21] were associated with five year survival of HIV patients on ART.ConclusionAll people living with HIV/AIDS should initiate ART as early as possible. Initiation of ART at the early stages of the disease, before deterioration of the functional status of the patients and before the reduction of CD4 counts and hemoglobin levels with an intensified health education on adherence to ART regimen is recommended.

Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect.

We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm³ randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm³, 88 % had plasma HIV RNA ≤ 400 copies/mL, and mean QNPZ-5 was -0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P < 0.001 for increase and P = 0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours.

Factors Impacting Early Mortality in Tuberculosis/HIV Patients: Differences between Subjects Naïve to and Previously Started on HAART

BackgroundMortality among patients with tuberculosis (TB)/HIV is highest during the first few months of antituberculous therapy. The objective of this study was to assess the factors associated with early mortality among TB/HIV patients and whether these factors are similar for HAART naïve and those with prior HAART initiation.MethodsProspective cohort study including HIV patients with tuberculosis confirmed by culture, cared for at a referral center in Rio de Janeiro, Brazil. Multivariable Cox analysis was used to assess predictors of mortality within 3 months of antituberculous therapy.ResultsAmong 227 patients included, 90 (40%) started HAART before TB diagnosis. The median time to TB diagnosis after ARV initiation was 5.9 months (interquartile range [IQR] 3.0–8.9 months). Fourteen patients (6%) died within the first 3 months. Mortality was not different between patients previously started on HAART and those who were naïve to it. In the overall adjusted analysis, HAART use during TB treatment (hazard ratio [HR] = 0.21, 95% confidential interval [CI] = 0.06–0.72) and CD4 lymphocyte count >100 cells/mm3 (HR = 0.21, 95% CI = 0.04–0.99) were associated with lower mortality, while subjects with unknown baseline CD4 lymphocyte count (HR = 9.39, 95% CI = 2.56–34.5) had higher mortality. In subgroup analysis, among HAART naïve subjects, disseminated TB (HR = 5.32, 95% CI = 1.09–25.8) and unknown baseline CD4 lymphocyte count (HR = 13.2, 95% CI = 2.71–64.5) were associated with significantly higher mortality, while HAART (HR = 0.14, 95% CI = 0.03–0.69) predicted a better outcome. Among subjects previously started on HAART, mortality was significantly associated with duration of TB symptoms >120 days (HR = 6.15, 95% CI = 1.15–32.9).ConclusionsPredictors of early mortality among TB/HIV patients may vary according to the timing of HAART initiation. Among HAART naïve patients, mortality was influenced by baseline clinical severity, HAART use and, possibly, the quality of care preceding TB diagnosis. For patients with prior HAART initiation, longer delays in TB diagnosis predicted a significantly higher mortality.

An Optimal Body Mass Index Range Associated With Improved Immune Reconstitution Among HIV-Infected Adults Initiating Antiretroviral Therapy

Higher body mass index (BMI) was associated with slower human immunodeficiency virus (HIV) disease progression before the availability of effective antiretroviral therapy (ART), but the relationship between pretreatment BMI and CD4(+) lymphocyte recovery on ART is not well described. We conducted an observational cohort study of HIV-infected, ART-naive adults starting treatment at a clinic affiliated with Vanderbilt University in Nashville, Tennessee. We assessed the relationship between pretreatment BMI and CD4(+) lymphocyte count change from baseline to 12 months in all subjects, among those with plasma HIV-1 RNA levels <400 copies/mL for ≥ 6 months and those with <10% change in weight during follow-up. Linear regression models were adjusted for age, sex, race, protease inhibitor usage, year of ART initiation, and baseline CD4(+) lymphocyte count and HIV-1 RNA level. A total of 915 patients met inclusion criteria; 78% were male, and their median age, BMI, and CD4(+) lymphocyte count were 39 years, 24 kg/m², and 171 cells/μL, respectively. The CD4(+) lymphocyte increase at 12 months was greatest among patients with a pretreatment BMI of ~25-30 kg/m² and diminished above and below this range (P = .03). Similar patterns were observed in the subgroup analyses. Among patients with a pretreatment CD4(+) lymphocyte count < 200 cells/μL, a BMI of ~25 kg/m² was associated with the highest odds of reaching a CD4(+) lymphocyte count > 350 cells/μL at 12 months (P = .05). 12-month immune reconstitution on ART was highest among patients commonly classified as overweight, suggesting there may be an optimal BMI range for immune recovery on ART.

Immunological profile in persons under antiretroviral therapy in a rural Nigerian hospital.

Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in sub-Saharan Africa, with Nigeria having the third highest burden of HIV infection globally; efforts are made to increases access to HIV/AIDS care and treatment. This has currently reached rural areas with limited manpower and laboratory evaluation capacity. This review is necessitated by the paucity of interim report on treatment profile in Nigerian rural areas. We report on the immunological profile of patients on antiretroviral therapy (ART) in Otukpo General Hospital, a rural Nigerian hospital. This is a retrospective cohort study of patients receiving ART treatment and care, on April 2009, when 2347 patients were under ART therapy. Out of these, 96 patients were selected by simple random sampling from hospital register, with their data abstracted from standardized Ministry of Health registers and facility documents kept at the hospital, and analyzed for descriptive and biometric measures. Ninty-six patients (29% males) with a median age of 35 years, median baseline CD4 lymphocyte count 221 cells/mL, median one year CD4 lymphocyte count of 356 cells/mL and median one year CD4 lymphocyte increment of 124 cells/mL were studied. There is no statistically significant difference in baseline CD4 lymphocyte count when data is disaggregated by type of drug regimen (AZT, D4T and TDF). Fourty-four percent, 23% and 33% of patients were on TDF, D4T & AZT based regimen, respectively (P=0.66). Increment of >100 cells/mL was seen in 64.58% of the reviewed patients. There was a higher CD4 lymphocyte count increment in patients on TDF & D4T compared with those in AZT based regimens (ANOVA; P<0.0003). Multivariate linear regression model showed one year CD4 lymphocyte count, one year increment in CD4 lymphocyte count, WBC count, and absolute neutrophil count to be significant correlates of baseline CD4 lymphocyte count (P<0.0001). Equally, multivariate logistic regression found age, platelet count and CD4 lymphocyte count at 12 months showed to be significant predictors of CD4 lymphocyte increment above 100 cells/µL (P<0.0001). Despite advanced disease presentation and a very large-scale program, high quality HIV/AIDS care was achieved as indicated by good short-term, immunologic outcomes, while TDF & D4T induce higher immunological recovery compared with AZT. This report suggests that quality HIV care and treatment can be effective despite the challenges of a resource-limited setting.

Immunological profile in persons under antiretroviral therapy in a rural Nigerian hospital

Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in sub-Saharan Africa, with Nigeria having the third highest burden of HIV infection globally; efforts are made to increases access to HIV/AIDS care and treatment. This has currently reached rural areas with limited manpower and laboratory evaluation capacity. This review is necessitated by the paucity of interim report on treatment profile in Nigerian rural areas. We report on the immunological profile of patients on antiretroviral therapy (ART) in Otukpo General Hospital, a rural Nigerian hospital. This is a retrospective cohort study of patients receiving ART treatment and care, on April 2009, when 2347 patients were under ART therapy. Out of these, 96 patients were selected by simple random sampling from hospital register, with their data abstracted from standardized Ministry of Health registers and facility documents kept at the hospital, and analyzed for descriptive and biometric measures. Ninty-six patients (29% males) with a median age of 35 years, median baseline CD4 lymphocyte count 221 cells/mL, median one year CD4 lymphocyte count of 356 cells/mL and median one year CD4 lymphocyte increment of 124 cells/mL were studied. There is no statistically significant difference in baseline CD4 lymphocyte count when data is disaggregated by type of drug regimen (AZT, D4T and TDF). Fourty-four percent, 23% and 33% of patients were on TDF, D4T &amp; AZT based regimen, respectively (P=0.66). Increment of &gt;100 cells/mL was seen in 64.58% of the reviewed patients. There was a higher CD4 lymphocyte count increment in patients on TDF &amp; D4T compared with those in AZT based regimens (ANOVA; P&lt;0.0003). Multivariate linear regression model showed one year CD4 lymphocyte count, one year increment in CD4 lymphocyte count, WBC count, and absolute neutrophil count to be significant correlates of baseline CD4 lymphocyte count (P&lt;0.0001). Equally, multivariate logistic regression found age, platelet count and CD4 lymphocyte count at 12 months showed to be significant predictors of CD4 lymphocyte increment above 100 cells/µL (P&lt;0.0001). Despite advanced disease presentation and a very large-scale program, high quality HIV/AIDS care was achieved as indicated by good short-term, immunologic outcomes, while TDF &amp; D4T induce higher immunological recovery compared with AZT. This report suggests that quality HIV care and treatment can be effective despite the challenges of a resource-limited setting.

Risk factors for incident diabetes mellitus among HIV‐infected patients receiving combination antiretroviral therapy in Taiwan: a case–control study

Recent studies suggest that patients with HIV infection are at increased risk for incident diabetes mellitus (DM). We investigated the incidence and risk factors of DM among HIV-infected patients receiving combination antiretroviral therapy (CART) in Taiwan. Incident cases of DM were identified among HIV-infected patients at the National Taiwan University Hospital between 1993 and 2006. A retrospective case-control study was conducted after matching cases with controls for sex, age at HIV diagnosis, year of HIV diagnosis, mode of HIV transmission and baseline CD4 lymphocyte count. A multivariate analysis was performed to identify risk factors for incident DM among HIV-infected patients. In 824 HIV-infected patients eligible for analysis, 50 cases of incident DM were diagnosed, resulting in an incidence of 13.1 cases per 1000 person-years of follow-up. In total, 100 matched controls were identified. Risk factors for incident DM were a family history of DM [odds ratio (OR) 2.656; 95% confidence interval (CI) 1.209-5.834], exposure to zidovudine (OR 3.168; 95% CI 1.159-8.661) and current use of protease inhibitors (OR 2.528; 95% CI 1.186-5.389). Incident DM was associated with a family history of DM, exposure to zidovudine and current use of protease inhibitors in HIV-infected patients receiving CART in Taiwan.

Baseline CD4 lymphocyte count among HIV patients in Kano, Northern Nigeria

HIV causes immunodeficiency by infection, lyses and depletion of CD4 T-lymphocytes; hence CD4 count has become a valuable indicator of immune function in the management of HIV infection. Consequently, we evaluated baseline CD4 counts of 500 HIV seropsitive adults in a government sponsored anti-retroviral treatment (ART) scheme at our centre, for the purpose of monitoring subsequent response to anti-retrovirals. The overwhelming majority (92%) of our patients were within the sexually active, 3rd to 5th decade age group, and the mean CD4 count was 302 cells/μl. Half of our patients (251 cases) had AIDS as defined by CD4 count African Journal of Health Sciences Vol. 14 (3-4) 2007: pp. 212-215

Pregnancy and HIV Disease Progression during the Era of Highly Active Antiretroviral Therapy

Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.

Selective Drug Taking During Combination Antiretroviral Therapy in an Unselected Clinic Population

Multidrug therapy is necessary to achieve sustained viral suppression. Discordant adherence to individual components of a multidrug regimen may lead to adverse outcomes. Antiretroviral-naive patients initiating therapy from 1997 through 2002 were included. Adherence for each antiretroviral was determined using pharmacy refill data. Selective drug taking was defined as > or =5% difference in adherence between 2 components of an antiretroviral regimen lasting at least 60 days. A total of 322 of 415 patients (78%) met inclusion criteria. Selective drug taking occurred in 47 of 322 patients (15%) and on 51 of 438 regimens (12%). Factors associated with selective drug taking were lower baseline CD4 lymphocyte count (adjusted odds ratio [AOR]: 1.3, 95% CI: 1.1 to 1.6 per 100 cell/microL decrease); 3 times daily dosing schedule (AOR: 4.1, 95% CI: 1.1 to 15.5); and the presence of significant adverse drug events (AOR: 2.9, 95% CI: 1.3 to 6.4). Regimens containing a fixed-dose combination dosage form were less likely to have selective drug taking (AOR: 0.5, 95% CI: 0.2 to 0.99). Outcomes independently associated with selective drug taking included earlier progression to a new AIDS-defining illness or death (hazard ratio: 2.3, 95% CI: 1.2 to 4.5). Selective drug taking was relatively common among patients taking combination antiretroviral therapy. The factor most closely associated with selective drug taking was the presence of an adverse drug event. Clinical outcomes appeared worse in patients with selective drug taking.

Acquired Rifamycin Resistance with Twice-Weekly Treatment of HIV-related Tuberculosis

Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study. To evaluate the activity of intermittent rifabutin-based therapy. Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid. Culture-positive treatment failure or relapse. A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35-175) and 5.3 log10 copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4 < 100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs. Intermittent rifabutin-based therapy for HIV-related TB was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts.

Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa.

A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count < 200 x 10 cells/l. The programme used standardized protocols (using generic medicines whenever possible), a team-approach to clinical care and a patient-centred approach to promote adherence. Two-hundred and eighty-seven adults naive to prior ART were followed for a median duration of 13.9 months. The median CD4 lymphocyte count was 43 x 10 cells/l at initiation of treatment, and the mean log10 HIV RNA was 5.18 copies/ml. The HIV RNA level was undetectable (< 400 copies/ml) in 88.1, 89.2, 84.2, 75.0 and 69.7% of patients at 3, 6, 12, 18 and 24 months respectively. The cumulative probability of remaining alive was 86.3% at 24 months on treatment for all patients, 91.4% for those with a baseline CD4 lymphocyte count > or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.

Pilot Study to Enhance HIV Care Using Needle Exchange-Based Health Services for Out-of-Treatment Injecting Drug Users

The introduction of highly active antiretroviral therapy (HAART) has resulted in marked reductions in mortality and acquired immunodeficiency syndrome (AIDS) incidence across all risk groups; however, the proportionate decrease among injecting drug users (IDUs) has been less impressive. Much of the disparity in benefit to IDUs has been a consequence of decreased access to and receipt of potent antiretroviral combinations. Strategies to increase access to and utilization of HAART have included entry into drug treatment and abstinence. Unfortunately, as few as 15%-20% of active drug users in the United States, and in many other countries, are in drug treatment at any one time. We report a pilot project among out-of-drug treatment IDUs infected with human immunodeficiency virus (HIV); HIV therapy was successfully provided to active heroin injectors using the Community Health Care Van (CHCV) at sites of needle exchange. Subjects were willing to initiate, but were not receiving, recommended HIV therapy and were not interested in formal drug treatment. Antiretroviral therapy regimens were selected and linked to heroin injection timing. Weekly visits were scheduled by CHCV staff to assess adverse side effects and encourage adherence. Of the 13 participants, the mean baseline HIV-1 RNA level and CD4 lymphocyte count were 162,369 (log 5.21) copies per milliliter and 265 cells per milliliter, respectively. By 6 months, the proportion whose HIV-1 RNA was below the limits of detection (<400 copies/mL) was 85% (N=11); 77% (N=10) had nondetectable levels by 9 months. By 12 months, 54% (N=7) had a persistently nondetectable viral load, and the net increase in CD4 lymphocyte count was 150 cells per milliliter. As an additional and unintended benefit of this pilot project, 9 (69%) subjects chose to enter drug treatment after achieving a nondetectable viral load. Entry into drug treatment was associated with durability of viral suppression. This small pilot study suggests that health services based on needle exchange may enhance access to HAART among out-of-treatment HIV-infected IDUs. In addition, it demonstrates that this population can benefit from this therapy with the support of a nontraditional, community-based health intervention.

Highly active antiretroviral therapy outcomes in a primary care clinic

This paper compares antiretroviral outcomes of patients at a primary care clinic with those previously reported at HIV specialty clinics and examines risk factors for treatment failure. A retrospective medical record review was undertaken at an academic primary care practice in Baltimore, Maryland. One hundred and twenty-three patients were included who had not previously received HAART and who were started on a regimen that included a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor and at least one other new antiretroviral medication. HIV RNA levels, CD4 lymphocyte counts, missed appointment rate, HAART regimen, demographic variables, and their association with the achievement of a viral RNA of 500 or less at 7-14 months were analyzed. Forty-seven per cent of the patients had an HIV RNA level of 500 or less at 7-14 months after initiation of HAART. Factors associated with treatment failure included missed appointment rate, injection drug use and previous exposure to antiretroviral medication. On multivariate analysis, only missed appointment rate and lower baseline CD4 lymphocyte count were independently associated with treatment failure. The antiretroviral outcomes of patients started on HAART by experienced health care providers in this primary care practice were comparable to those reported in specialty clinics. As with previous reports, most patients did not maintain viral suppression. Missed appointment rate was the most important risk factor for treatment failure.