Weeks Of Highly Active Antiretroviral Therapy Research Articles

DISSEMINATED HISTOPLASMOSIS IN A PATIENT WITH NEWLY DIAGNOSED AIDS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Disseminated Histoplasmosis (DH) is an AIDS-defining illness caused by the dimorphic fungus Histoplasma capsulatum. Outbreaks have been associated with exposure to bird or bat droppings and amongst construction workers. It remains unclear whether DH represents an acute infection or a reactivation of latent infection. We present a case of DH in a newly diagnosed AIDS patient. CASE PRESENTATION: A 50 year old male Hispanic construction worker presented with a month history of persisting fever, chills, diaphoresis, progressive shortness of breath on exertion, non-bloody diarrhea and 15lbs weight loss. HIV screen was positive (new diagnosis) and his CD4+ cell count was 3 per cubic millimeter with a viral load of over 1 million copies/ml. CXR showed diffuse interstitial infiltrates in both lung fields and CT chest showed numerous punctate miliary pattern pulmonary nodules in the lungs with necrotic appearing lymph nodes in the proximal jejunal mesentery. SARS-CoV2 PCR was negative. BAL culture grew Histoplasma capsulatum, Lung biopsy pathology showed broad based budding yeast and urine histoplasma antigen was positive at greater than 23 ng/ml. He was treated with highly active antiretroviral therapy (HAART), IV liposomal amphotericin, and steroid. Empiric anti-TB therapy was stopped with negative quantiferon TB gold, BAL AFB smear and BAL MTB complex PCR. Silver stain for PCP, serum cryptococcal antigen, serum galactomammanan and fungitell assays were all negative. Hospital course was complicated by pneumothorax, septic shock, line related bloodstream infections that resolved with line removal and antimicrobials. Despite appropriate antifungal therapy for 40 days with decrease in his urine histoplasma antigen to 11 ng/ml, and HIV viral load decreasing to 330 copies/ml after 3 weeks of HAART, he remained ventilator dependent, on chest tubes and could not be weaned off sedation. His family made him comfort care only on hospital day 43 and he died peacefully after. DISCUSSION: Histoplasmosis has been recognized as an opportunistic infection in patients with AIDS and typically presents as disseminated disease. DH in conjunction with HIV infection is particularly common among Hispanic persons in the United states. In AIDS patients, DH is associated with a nonspecific clinical presentation—usually unexplained fever and weight loss. Histoplasmosis causes significant morbidity and mortality. Fungal infections deaths in AIDS were estimated at more than 700, 000 deaths (47%) annually. The frequent occurence of histoplasmosis with other opportunistic infections especially tuberculosis requires that tuberculosis be ruled out even if histoplasmosis is diagnosed. CONCLUSIONS: This case highlights the fact that although miliary pattern on CT Chest typically signifies tuberculosis, it can also be seen in histoplasmosis. Also associated morbidity and mortality of DH remains high in AIDS patients not on HAART. REFERENCE #1: Rana A. Hajjeh. Disseminated Histoplasmosis in Persons Infected with Human Immunodeficiency Virus. Clinical Infectious Diseases 1995; 21(Suppl 1):S108 -10. REFERENCE #2: Stuart M. Levitz, and Eugene J. Mark. Case 38-1998 — A 19-Year-Old Man with the Acquired Immunodeficiency Syndrome and Persistent Fever. N Engl J Med 1998; 339:1835-1843. REFERENCE #3: David W. Denning. Minimizing fungal disease deaths will allow the UNAIDS target of reducing annual AIDS deaths below 500 000 by 2020 to be realized. Philos Trans R Soc Lond B Biol Sci. 2016 Dec 5;371(1709). DISCLOSURES: No relevant relationships by Oluwadamilola Adeyemi, source=Web Response No relevant relationships by Ingrid Gils, source=Web Response No relevant relationships by Drew Ludwig, source=Web Response No relevant relationships by Biana Modilevsky, source=Web Response

Immunologic and virologic failure after first-line NNRTI-based antiretroviral therapy in Thai HIV-infected children

BackgroundThere are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART.MethodsAntiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count ≥30% from baseline. VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF.Results107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5) log10copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%≥25%) and 75% of children had HIV-RNA <1.7log10copies/ml.Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively.Only 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and specificity was 100 (93.9-100)%.ConclusionImmunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure.Trial RegistrationClinicaltrials.gov identification number NCT00476606

Comparison of HIV-Infected Patients' Characteristics and Clinical Outcomes Between Cohort-Dependent and Independent Patients: Korean HIV Cohort Study

Comparison of HIV-Infected Patients' Characteristics and Clinical Outcomes Between Cohort-Dependent and Independent Patients: Korean HIV Cohort Study

Response to Antiretroviral Therapy in HIV-Infected Ugandan Children Exposed and Not Exposed to Single-Dose Nevirapine at Birth

To compare the response to a nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in HIV-infected Ugandan children, exposed and nonexposed to single-dose NVP (sd NVP) at birth. HIV-infected study children were initiated on stavudine/lamivudine/NVP as a fixed dose combination. CD4 cell percent and HIV-1 RNA were documented at baseline, 12, 24, 36, and 48 weeks post-initiation of HAART. Ninety-two children were enrolled in the study, 44 in the sd NVP-exposed and 48 in the nonexposed cohort. The median age at enrollment was 1.7 years [interquartile range (IQR) 1.2-2.4] and 7.8 years (IQR 5.9-9.2) in the sd NVP-exposed and nonexposed cohorts,respectively (P < 0.001). At baseline and week 48 post-HAART, the median CD4 cell percentages were 14% and 33% for the NVP-exposed group and 8% and 22.5% in the nonexposed group (P < 0.0001). The median (IQR) viral load at baseline was 650,568 (359,979-2,086,613) RNA copies/mL and 239,027 (105,904-494,813) RNA copies/mL in the NVP-exposed and nonexposed cohorts, respectively. After 48 weeks of HAART, 76% of the NVP-exposed and 80% of the nonexposed children had a median viral load of < 400 copies/mL (P = 0.74). Both HIV-infected Ugandan older infants and children that were exposed and not exposed to sd NVP at birth had favorable treatment outcomes on NVP-containing HAART.

Prevalence and Persistence of Cervical Human Papillomavirus Infection in HIV-Positive Women Initiating Highly Active Antiretroviral Therapy

To determine the prevalence of human papillomavirus (HPV) DNA in cervical specimens from treatment-naive women initiating highly active antiretroviral therapy (HAART) and explore the longitudinal association of HPV DNA with CD4 count and HIV viral load (VL). Women enrolled before HAART were evaluated at baseline, weeks 24, 48, and 96 with CD4 count, VL, and cervical swab for HPV DNA. The 146 subjects had a median CD4 count of 238 cells per microliter and VL of 13,894 copies per milliliter. Ninety-seven subjects (66%) had HPV DNA detected in the baseline specimen including 90 subjects (62%) positive for 1 or more high-risk HPV types. HPV DNA detection declined to 49% at week 96 and that of a high risk HPV type to 39%. The duration of follow-up was associated with decreased detection of HPV DNA of any type (P = 0.045) and of high-risk HPV types (P = 0.003). There was at most a marginal association between HAART response and loss of detection of cervical HPV DNA. Women initiating HAART had a high prevalence of cervical HPV DNA that declined over 96 weeks of HAART. The relationship of CD4 count and VL response to the decline of cervical HPV DNA was not strong.

Pattern and Predictors of Immunologic Recovery in Human Immunodeficiency Virus-Infected Children Receiving Non-Nucleoside Reverse Transcriptase Inhibitor-Based Highly Active Antiretroviral Therapy

Non-nucleoside reverse transcription inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) is the recommended first-line regimen for children in Thailand. This study was aimed to assess pattern and predictors of immune recovery in antiretroviral-naive Thai children starting NNRTI-based HAART. Records were extracted from clinical databases of 2 treatment cohorts in Thailand. The inclusion criteria were HIV-infected naive children who initiated NNRTI-based HAART when CD4 <25%. Immune recovery was defined as achieving a target CD4% of 25. The impact of age, gender, baseline clinical category, CD4 and HIV RNA titer, and regimen on immune recovery to weeks 96 was assessed using multiple logistic regression. There were 274 patients (52% females) with a median baseline age of 7 (Interquartile range [IQR]: 4-9) years and a median CD4% of 5 (IQR: 1-12) who started treatment with nevirapine (66%) or efavirenz (34%) based HAART. Median duration of follow-up was 168 (IQR: 120-192) weeks. The median CD4% increase from baseline was 7% (IQR: 5-11) and 18% (IQR: 12-23) at weeks 24 and 96, respectively. The probability of reaching target CD4% was 51% (95% confidence interval: 45%-57%) by week 96. The predictors of immune recovery at week 96 were younger age, female gender, higher baseline CD4%, and sustained virologic suppression after week 24. In this cohort of children with low baseline CD4, half achieved immune recovery after 96 weeks of HAART. The predictors for immune recovery are younger children, female gender, high baseline CD4%, and long-term virologic suppression.

Quality of life and the impact of drug toxicities in a South African community-based antiretroviral programme.

BackgroundThe impact of highly active antiretroviral therapy (HAART) on health-related quality of life has been widely researched in the developed world, but there are few data from sub-Saharan Africa, where the vast majority of HIV-infected individuals live. This study examined health-related quality of life among HIV-positive individuals initiating HAART in Cape Town, South Africa, and explored the impact of HAART-related drug toxicities on quality of life.MethodsHealth-related quality of life was assessed using a standardised questionnaire, the Medical Outcomes Survey Short Form 36. Physical health summary scores and mental health summary scores were compared pre-HAART and at regular intervals during the first 48 weeks of HAART. The relationships between socio-demographic, baseline and on-treatment variables and decline in health-related quality of life, as well as the impact of drug toxicities on quality of life, were assessed in unadjusted bivariate and adjusted multivariate analyses.ResultsTwo hundred and ninety-five patients were enrolled into the study. There was a significant increase in health-related quality of life during the first 48 weeks on HAART. The median physical health summary score increased from 45 to 53 units (p < 0.001) and median mental health summary score increased from 45 to 50 units (p < 0.001).The bulk of this increase occurred during the first 16 weeks. Overall, 23% of participants experienced a decline in their physical health summary score, while 34% showed a decline in the mental health summary score. Average drops in median physical and mental health summary scores were 8.4 units (SD 9.31) and 9.9 (SD 11.4) units respectively. Participants with drug toxicity had lower physical health summary scores than participants without drug toxicity at all time points. However, only three participants with toxicity (27%) reported an actual decline in health-related quality of life by week 48. Drug toxicities had little impact on mental health summary scores.ConclusionThese results confirm the health-related quality of life benefits of HAART. While the majority of patients experienced a significant improvement in health-related quality of life on HAART, up to a third of patients reported declines in this quality of life. This was largely related to better baseline clinical state. HAART-related drug toxicities did not have a significant impact on health-related quality of life during the first year of HAART, which supports the ongoing use of the current national first-line regimen.

Hepatitis B Virus Infection and Response to Antiretroviral Therapy (ART) in a South African ART Program

Coinfection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is common in Africa; however, the impact of HBV infection on the outcomes of antiretroviral therapy programs is unclear. We evaluated the impact of chronic hepatitis B on HIV virologic response, changes in CD4 cell count, hepatotoxicity, and mortality among Africans receiving highly active antiretroviral therapy (HAART). We conducted a retrospective cohort study involving a workplace HAART program in South Africa. Participants received HAART according to a protocol and were followed up for up to 72 weeks. On the basis of pre-HAART serum assays, patients were classified as being hepatitis B surface antigen (HBsAg) negative, HBsAg positive with a low HBV DNA level (</= 1 x 10(4) copies/mL), and HBsAg positive with a high HBV DNA level (> 1 x 10(4) copies/mL). The relationships between HBV status and HIV RNA suppression, change in CD4 cell count, mortality, and hepatotoxicity were assessed with use of regression techniques. Five hundred thirty-seven individuals fulfilled the inclusion criteria; 431 (80.3%) of these patients were HBsAg negative, 60 (11.2%) were HBsAg positive with a low HBV DNA level, and 46 (8.6%) were HBsAg positive with a high HBV DNA level. All groups had similar rates of HIV RNA suppression (P = .61), CD4 cell count increases (P =.75), and mortality (17 total deaths; P=.11) for up to 72 weeks after the initiation of HAART. Baseline transaminase levels were highest in the group with high HBV DNA levels (P=.004). Hepatotoxicity was similar between the HBsAg-negative group and the group with low HBV DNA levels but was higher in the group with high HBV DNA levels (incidence rate ratio, 4.4). We revealed that HBV status does not affect HIV RNA suppression, CD4 cell count response, or mortality during the first 72 weeks of HAART in an African setting. The risk of HBV-associated hepatotoxicity, however, is associated with the baseline HBV DNA level.

Safety and Efficacy of Initiating Highly Active Antiretroviral Therapy in an Integrated Antenatal and HIV Clinic in Johannesburg, South Africa

To describe the safety and efficacy of highly active antiretroviral therapy (HAART) in pregnant women treated in an integrated antiretroviral antenatal clinic (ANC ARV). A retrospective analysis was performed on patients attending the ANC ARV from August 2004 through February 2007. Data were collected on 689 treatment-naive pregnant women initiated on HAART. The mean age was 29.2 years. The mean baseline CD4 count was 154 cells per microliter, and mean baseline HIV viral load was 101,561 copies per milliliter. Tuberculosis was the most prevalent presenting opportunistic infection (7.7%). Stavudine, lamivudine, and nevirapine were initiated in 82% of women with the most frequent adverse drug reaction being nevirapine-associated skin rash (3.5%). Mean gestational age at HAART initiation was 27 weeks. Among women with follow-up data, 80% gained 50 or more CD4 cells per microliter and 80.5% achieved viral suppression to <1,000 copies per milliliter. Of 302 mother-infant pairs who completed postnatal follow-up, the HIV transmission rate was 5%. In women who received more than 7 weeks of HAART during pregnancy, transmission was 0.3%. Within the ANC ARV program, initiating pregnant women on HAART was feasible, safe, and effective. Advanced gestational age at treatment initiation and loss to follow-up emerge as important challenges in this population.

Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy

Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechanisms. During recent years it has become evident that a subpopulation of T cells [T regulatory (T(regs))] play a major role in sustaining tolerance to self-antigens. To investigate the influence of initiation of highly active anti-retroviral therapy (HAART) on the T(reg) level in HIV-infected patients we have conducted a prospective study enrolling treatment-naive HIV-infected patients just prior to starting treatment with HAART, measuring levels of T(regs) by flow cytometry and mRNA expression of forkhead box P3 (FoxP3) at weeks 0, 4, 12 and 24 of treatment. In this prospective study neither the percentage of CD4(+)CD25(high+) nor the expression of FoxP3 changed significantly during 24 weeks of HAART. Furthermore, HIV patients have higher T(regs) measured as percentages of CD4(+)CD25(high+) cells paralleled by higher levels of FoxP3 compared with healthy controls. The elevated level of T(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients.

Case Report: Bilateral Renal Aspergillosis in a Patient with AIDS: A Case Report and Review of Reported Cases

Renal aspergillosis is an extremely uncommon complication in HIV-infected patients. In general, prognosis is poor and the need for nephrectomy is emphasized. We report the case of a 37-year-old patient with AIDS since April 2003 (CD4 count 10 cells/mm(3), a high viral load, Candida esophagitis, bilateral pneumonia, HIV encephalopathy). Treatment with zidovudine, lamivudine, nevirapine, and lopinavir/ritonavir was started. Adherence to this medication proved to be a problem, but after 18 weeks of HAART the CD4 count was 110 cells/mm(3) and viral load was undetectable. One year later, he presented with hematuria and flank pain. Computed tomography (CT) scan revealed multiple lesions in both kidneys. Cultures of the abscess aspirates yielded Aspergillus fumigatus. Our review of 18 reported cases shows that prognosis of renal aspergillosis is poor if nephrectomy is not performed. However, in the present case a conservative approach was chosen to avoid life-long dialysis. The patient was treated successfully with a combination of voriconazole, percutaneous drainage, and highly active antiretroviral therapy (HAART). Renal function was completely preserved. Reported cases from the literature of renal aspergillosis in HIV-infected patients are summarized in this paper.

SUSTAINED IMMUNOLOGIC AND VIROLOGIC EFFICACY AFTER FOUR YEARS OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS INFECTED CHILDREN IN THAILAND

We report the long-term efficacy of highly active antiretroviral therapy (HAART) in 107 antiretroviral-naive human immunodeficiency virus (HIV)-infected Thai children. In an intention-to-treat analysis, 70% of the children had undetectable HIV RNA titers after 192 weeks of HAART. The mean CD4 cell percentage increased from 5.3% to 26.6%. HAART is effective for HIV-infected children in this resource-poor setting despite initiation of treatment in the advanced stage of disease.

Changes in Immunohaematological Characteristics of Human Immunodeficiency

Highly active anti-retroviral therapy (HAART) has changed the mode of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) care in the developed countries, but its benefits and effects have not been well elucidated in Nigeria. In this case-control study, we have investigated the immediate effects of HAART with stavudine, lamivudine and nevirapine on the haematological and immunological parameters of 70 antiretroviral naïve, HIV-positive subjects during the first 8 weeks of therapy. Thirty HIV-positive antiretroviral naïve individuals not yet on HAART were included as controls. At baseline, treated subjects and controls did not differ significantly in their haematological and immunological parameters. After 8 weeks of HAART, the differences in mean haemoglobin (t = 5.77, p

Incidence and prevalence of the metabolic syndrome in a cohort of naive HIV-infected patients: Prospective analysis at 48 weeks of highly active antiretroviral therapy

We undertook a prospective study to assess the prevalence of the metabolic syndrome (MetS) in HIV patients at the start of highly active antiretroviral therapy (HAART), and at 48 weeks, and we also studied its relationship with high-sensitivity C-reactive protein (hs-CRP) in 60 HIV patients who maintained the same regimen during follow-up. The prevalence of MetS rose from 16.6% at baseline to 25% at 48 weeks (P=0.0001). During follow up, 7/50 patients developed MetS, leading an incidence of 14/100 patients/year. The MetS was associated with age, homosexuality, and lower hepatitis C virus prevalence; only age remained significant in the multivariate analysis (for each five-year increase: beta coefficient 4.26, 95% confidence interval, 3.80-4.75; P=0.0039). The hs CRP values were similar in patients with and without the MetS, and they did not increase at 48 weeks of HAART.

Hospitalization and Mortality among HIV-Infected Children after Receiving Highly Active Antiretroviral Therapy

Pediatric antiretroviral therapy programs have recently been implemented in resource-limited settings. Their impact in a prospective cohort is not well documented. The aim of this study was to evaluate the rates and causes of hospitalization and mortality among human immunodeficiency virus (HIV)-infected Thai children after receiving highly active antiretroviral therapy (HAART). Children who started receiving HAART from August 2002 to March 2005 were prospectively observed. The patients included in the study were antiretroviral-naive HIV-infected children who had CD4 cell percentages < or =15% before treatment. All patients were observed for at least 48 weeks. One hundred ninety-two children were included. The mean age at HAART initiation was 7.6 years (range, 0.4-14.8 years). At baseline, the mean CD4 cell percentage (+/-SD) was 5.2%+/-4.9%, and the mean plasma HIV RNA level (+/-SD) was 5.4+/-0.5 log(10) copies/mL. Sixty-seven children (35%) were hospitalized a total of 108 times. The hospitalization rate decreased from 30.7% during the first 24-week period to 2.0% during weeks 120-144 after initiation of HAART. Fifty-nine hospital admissions (54.6%) occurred during the first 24 weeks of HAART. Causes of hospitalization were pneumonia and other bacterial infections (61.7%), immune reconstitution syndrome (23.4%), noninfectious illness (6.5%), opportunistic infection (5.6%), and drug-related events (2.8%). The mortality rate decreased from 5.7% in the first 24 weeks to 0%-0.6% in the subsequent 24-week intervals. Hospitalization and mortality rates significantly decreased among HIV-infected children receiving HAART. Most hospitalizations and deaths occurred during the first 24 weeks of HAART.

Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)

BackgroundThe association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied.ResultsThere were few primary PI associated mutations in this PI-naïve population, but 84% had NRTI mutations – codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017).ConclusionNo increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.

Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy

In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4+ T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART. To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4+ T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression. T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART. There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4+ T-lymphocyte percentages (P < .02) and naive CD4+ T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA. To maintain adequate levels of CD4+ T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4+ T lymphocytes in the presence of persistent virus. The TREC level is a useful marker of thymic function in HIV-infected children.

The effects of highly active antiretroviral therapy on the haemotological profile of HIV-infected Africans: the Nigerian perspective

Background and Objective: This short -term .....se control study of 70 consecutively recruited HIV-infected and previously antiretroviral naive patients, treated with a combination therapy of stavudine, lamivudine and nevirapine (case) and 30 HIV-infected patients who were yet to start therapy (controls) were studied to evaluate the effect of highly active antiretroviral therapy (HAART) on the haematological parameters of HIV infected individuals. Methodology: Haematological parameters of haemoglobin, total with cell count, platelet count, erythrocyte sedimentation rate and differentia/leucocyte count were determined at baseline for subjects and control patients. Subjects were placed on HAART (stavudine 40 mg, lamivudine 150mg and nevirapine 200mg) twice daily for twelve weeks. of haematological parameters was repeated after 12 weeks of HAART in subjects and untreated controls. Result: The occurrence of anaemia, neutropenia, thrombocytopenia and leucopenia obtained respectively at baseline was 84.3%, 24.3%, 11.4% and 11.4% for subjects but after 12 weeks of HAART these declined respectively to 75.7%, 7.1%, 5.7% and 1.4%. Comparatively, there was an increase from baseline values of 96.7%, 23.3%, 6.7% and 6.7% to 100%, 36.7%, 10% and 36.7% respectively in untreated controls. The difference in mean haematological values of subjects and controls at baseline was not statistically significant (p < O.OS). But after 12 weeks of HAART in subjects and observation in untreated controls, the difference in mean haemaglobin (t = 5.77, p < 0.05), platelet count (I= 2.25, p < 0.05) and erythrocyte sedimentation rate (t = -3.20 p < 0.05) became statistically significant. While the haemoglobin, platelet and erythrocyte sedimentation rate improved in subjects, it declined in untreated controls. Conclusion: This study clearly indicates that highly active antiretroviral therapy of two reverse transcriptase inhibitors (stavudine and lamivudine) and one noll -nucleoside reverse transcriptase inhibitor (nevirapine) may improve cytopenios in HIV-infected Nigerians and may be used in patients with haematologic intolerance to other regimen.

Impact of highly active antiretroviral therapy on blood pressure in HIV‐infected patients. A prospective study in a cohort of naive patients

To assess the impact of highly active antiretroviral therapy (HAART) on the blood pressure (BP) of naive patients after 1 year of treatment. A prospective, observational study of 95 HIV-positive patients in our Unit starting HAART between January 2001 and October 2002 and maintaining the same regimen for 48 weeks of follow-up was carried out. Data on blood pressure (BP) and demographic, epidemiological, clinical, immunovirological and therapeutic characteristics related to HIV infection were collected prior to HAART and at week 48. High blood pressure (HBP) [systolic BP (SBP) > or =140 mm Hg and/or diastolic BP (DBP) > or =90 mm Hg] was defined according to international criteria. Of the 95 patients, 78 were men, 44% had AIDS and 68% were smokers, and their mean age was 40 years. At week 48 the prevalence of HBP was 26% and SBP, DBP and pulse pressure (PP) increased (121.8 versus 116.6 mm Hg, P=0.0001; 76.3 versus 69.7 mm Hg, P=0.004; 46.9 versus 43.8 mm Hg, P=0.001, respectively). Univariate analysis showed that HBP was associated with older age, higher body mass index (BMI), higher baseline lipids, and higher baseline BP. A linear regression model adjusting for age and sex suggested a significant impact of older age, higher baseline SBP, higher baseline hypercholesterolaemia and lower baseline CD4-cell count on SBP increase. Blood pressure increased after 48 weeks of HAART, leading to an important prevalence of hypertension. The increase in SBP depended on age and baseline lipid profile and immunological status. BP should be periodically measured and treated when necessary in HIV-infected patients on HAART.

Impact of Hepatitis C Virus on Immune Restoration in HIV-Infected Patients Who Start Highly Active Antiretroviral Therapy: A Meta-analysis

There are conflicting data in the medical literature regarding the degree of immune restoration (as measured by CD4 cell count) in patients who commence highly active antiretroviral therapy (HAART) when coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), compared with those with HIV infection alone. We performed a meta-analysis that compared CD4 cell count increases after HAART initiation in HCV-negative and HCV-positive patients who were infected with HIV. Published studies in the English-language medical literature that involved cohorts of HCV-negative and HCV-positive patients who were coinfected with HIV were obtained by searching the Medline, Embase Drugs and Pharmacology, and EBM Review-Cochrane Central Register of Controlled Trials databases. Data were extracted independently from relevant studies by 3 investigators and were used in a fixed-effects meta-analysis to determine the mean difference in the expected CD4 count change in the 2 groups. Eight trials involving 6216 patients were analyzed. Patients with HIV-HCV coinfection had a mean increase in the CD4 cell count that was 33.4 cells/mm3 (95% CI, 23.5-43.3 cells/mm3) less than that for HIV-infected patients without HCV infection. The results of the meta-analysis were independent of any one study and were not influenced by the year in which HAART was started. This meta-analysis shows that patients with HIV-HCV coinfection do, in fact, have less immune reconstitution, as determined by CD4 cell count after 48 weeks of HAART, than do patients with HCV infection alone. Future research should examine whether an impaired immunologic response corresponds with meaningful virologic and clinical outcomes.