Human Immunodeficiency Virus RNA Concentration Research Articles

Alcohol consumption and HIV disease prognosis among virally unsuppressed in Rural KwaZulu Natal, South Africa

<abstract><sec> <title>Background</title> <p>The effect of alcohol consumption and human immunodeficiency virus (HIV) disease prognosis has been examined in several studies with inconsistent findings. We sought to determine the effect of alcohol consumption on HIV disease prognosis by examining CD4<sup>+</sup> T cell count/µL (CD4<sup>+</sup> count) and HIV RNA concentration [HIV viral load (VL)] independent of anti-retroviral therapy (ART).</p> </sec><sec> <title>Methods</title> <p>A secondary analysis was performed on a cross-sectional survey data of 1120 participants between 2018 and 2020. Questionnaires were used to obtain the participants' history of alcohol consumption. Blood samples were assayed for CD4<sup>+</sup> T cell count/µL (CD4<sup>+</sup> count) and HIV RNA concentration (HIV viral load). The history of alcohol consumption was categorized into non-alcohol consumers, non-heavy alcohol consumers, and heavy-alcohol consumers. Age, cigarette smoking, gender, and ART use were considered potential confounders. Participants were categorized into two cohorts for the analysis and a multivariate logistic regression was used to establish relationships among virally unsuppressed participants who were ART-experienced and ART-naïve.</p> </sec><sec> <title>Results</title> <p>A total of 1120 participants were considered for analysis. The majority were females (65.9%) between 15–39 years (72.4%). The majority were non-smokers and non-alcohol consumers (88% and 79%, respectively). ART-experienced females had an increased risk of having a higher VL (VL > 1000). This finding was statistically significant [RR, 0.425, 95% CI, (0.192–0.944), p-value, 0.036]. However, ART-experienced participants aged above 64 years had an increased risk of having a lower VL (VL < 1000 copies/mL) and a lower risk of having a higher VL (VL > 1000). However, ART-naïve participants aged between 40–64 years had a significantly lower risk of having higher CD4 count (CD4<sup>+</sup> > 500 cells) and an increased risk of having a lower CD4 count [OR, 0.566 95% CI, (0.386–0.829), p-value, 0.004]. History of alcohol consumption did not have a significant effect on CD4<sup>+</sup> cell count and VL in neither the ART-experienced nor the naïve cohort.</p> </sec><sec> <title>Conclusions</title> <p>Female middle-aged people living with HIV (PLWH) are more likely to have a poorer HIV disease state, independent of alcohol consumption. Alcohol consumption may not have a direct effect on CD4<sup>+</sup> cell count and VL in either ART-naïve or experienced patients.</p> </sec></abstract>

CXCL13 as a Cerebrospinal Fluid Marker for Neurosyphilis in HIV-Infected Patients With Syphilis

Asymptomatic neurosyphilis is more difficult to diagnose in human immunodeficiency virus (HIV)-infected patients because HIV itself can cause cerebrospinal fluid (CSF) pleocytosis. The proportion of CSF lymphocytes that are B cells is elevated in neurosyphilis, suggesting that the CSF concentration of the B cell chemoattractant, chemokine (C-X-C motif) ligand 13 (CXCL13) concentration may also be elevated. CSF and blood were collected from 199 HIV-infected patients with syphilis and neurosyphilis. Serum and CSF CXCL13 concentrations were determined. Patients with neurosyphilis had higher CSF and serum CXCL13 concentrations compared to patients with syphilis but not neurosyphilis. The odds of having symptomatic neurosyphilis were increased by 2.23-fold for every log increase in CSF CXCL13 concentration and were independent of CSF white blood cell and plasma HIV RNA concentrations, peripheral blood CD4+ T cell count and use of antiretroviral medications. A cut-off of 10 pg/mL CSF CXCL13 had high sensitivity and a cut-off of 250 pg/mL or evidence of intrathecal synthesis of CXCL13 had high specificity for diagnosis of both symptomatic and asymptomatic neurosyphilis. CSF concentrations of CXCL13 declined after treatment for neurosyphilis. CSF CXCL13 concentration may be particularly useful for diagnosis of neurosyphilis in HIV-infected patients because it is independent of CSF pleocytosis and markers of HIV disease.

Evaluation of Human Immunodeficiency Virus Type 1-Infected Chinese Patients Treated with Highly Active Antiretroviral Therapy for Two Years

The purpose of this study was to evaluate the long-term efficacy and safety of nevirapine in combination with didanosine and stavudine in the treatment of human immunodeficiency virus (HIV)1-infected Chinese patients in routine clinical practice. The study, from April 2003 to May 2005, with follow-up through 24 mo, was conducted at the Department of Infectious Diseases, Second Xiangya Hospital, Central-South University in Changsha, Hunan Province, China. Twenty-seven HIV1-infected patients received didanosine, stavudine, and nevirapine. Information from case notes regarding age, sex, side effects, viral load, naive and memory T cells, and CD4(+) and CD8(+) T cell count at baseline, 3, 6, 12, 18, and 24 mo was collected and analyzed. Virologic suppression, defined as an HIV RNA concentration of less than 50 copies/mL at months 3, 6, 12, 18, and 24, was considered the main outcome measure. Of 27 patients, 17 were men with a mean age 33.5 yr. The mean baseline viral load was 5.15 log copies/mL and the mean CD4(+) cell count was 185 cells/dL. Of 27 patients, 3 patients discontinued study medication; treatment was changed, because of side effects, from didanosine (ddI), stavudine (d4T), and nevirapine (NVP) to zidovudine, lamivudine, and NVP for 24 patients who had completed 24 mo of treatment with ddI, d4T, and NVP; and viral load suppression was attained in 17 patients (70.8%) at 12 mo, in 14 patients (58.3%) at 18 mo, and in 13 patients (56.6%) at 24 mo. The CD4 T cell count increased by 114 cells/microL (mean, 299 cells/microL) after 12 mo of treatment and by 132 cells/microL (mean, 317 cells/microL) after 24 mo of treatment. Naive T cells and memory cells also increased in number, but at a slower rate. Activated (CD38(+)) CD8(+) T cells were elevated at baseline (67.7%) and declined by month 24 (49.7%), but did not reach normal levels. We conclude that a regimen of NVP with ddI and d4T provided durable suppression of plasma viral load in HIV-infected patients, with significant improvement in the CD4 cell count, and can be well tolerated by patients with HIV-1 infection.

C-Reactive Protein Is a Marker for Human Immunodeficiency Virus Disease Progression

Limited data on acute-phase C-reactive protein (CRP) levels in human immunodeficiency virus (HIV) infection exist. We obtained a single measurement of CRP from 513 HIV-infected men in the Multicenter AIDS Cohort Study to examine the association between CRP and immune suppression and progression to AIDS. We estimated changes in CRP during the course of HIV infection in 81 of these individuals using specimens collected from October 1, 1984, to December 31, 1996. The cross-sectional associations between log(10) CRP were correlated inversely with CD4 lymphocyte counts (r=-0.17; P<.001) and directly with log10 HIV RNA levels (r=0.20; P<.001). Levels of CRP of more than 2.3 mg/L were associated with a decreased time to the development of AIDS (relative time to AIDS, 0.36; P<.001) compared with individuals with CRP levels of 1.2 mg/L or less, which remained significant after adjustment for CD4 lymphocyte counts and HIV RNA and hemoglobin concentrations. Levels of CRP significantly increased over time with mean slopes of 8.5% (95% confidence interval, 4.9%-12.2%) and 4.5% (95% confidence interval CI, 2.1%-6.9%) per year for individuals with and without progression to AIDS, respectively. Individuals had a geometric mean CRP level of 2.5 mg/L in the 6-month interval before progression to AIDS, which was an increase from a nadir of 1.0 mg/L at 6.5 years before progression to AIDS. Levels of CRP were associated with HIV disease progression independent of CD4 lymphocyte counts and HIV RNA levels. In addition, regardless of progression to AIDS, HIV-infected individuals had a significant increase in CRP over time. This may have implications for cardiovascular disease among HIV-infected individuals.

Sustained Efficacy of Nevirapine in Combination with Two Nucleoside Analogues in the Treatment of HIV-Infected Patients: A 48-Week Retrospective Multicenter Study

Background: Nevirapine, a nonnucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the durable suppression of HIV with nevirapine when used along with other nucleosides in HIV-infected patients who are treated in clinical practice needs further evaluation. Purpose: To evaluate the sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients in routine clinical practice. Design: A multicenter study from January 1997 to December 2000, with follow-up through 48 weeks, was conducted at four different genitourinary medicine clinics in the United Kingdom. Forty-four HIV-infected patients received nevirapine and two nucleoside analogues. Information from case notes regarding age, sex, side effects, viral load, and CD4 lymphocyte counts at baseline, 24 weeks, and 48 weeks was collected and analyzed. Virologic suppression, defined as HIV RNA concentration of less than 400 copies/mL at Weeks 24 and 48, was considered as the main outcome measure. Results: Out of 44 patients, 41 were men with a mean age of 39.3 years (95% CI 36.7-41.8). The baseline viral load was 2.11 × 102 to 9.74 × 105 copies/mL (median 7.7 × 104 and CD4 counts 6 to 605 cells/dL (M = 247; 95% CI 198-295). Of 39 patients who completed 48 weeks of treatment, viral load suppression was attained in 31 patients (79.4%; 95% CI 66.8-92.0) at 24 weeks and in 27 patients (69.2%; 95% CI 54-83) at 48 weeks. The CD4 lymphocyte count increased in 32 (82%) patients (mean 106 cells/dL, 95% CI 73-139, p = .0001, Wilcoxon signed rank test) after 24 weeks and in 33 (84.6%) patients (mean 160 cells/dL, 95% CI 115-204, p = .0001, Wilcoxon signed rank test) after 48 weeks of treatment. Of 20 patients whose baseline viral load was <100,000, 16 had viral load suppressed at 24 weeks and 15 at 48 weeks (p = .6, chi-square test). Conclusion: A regime of nevirapine with two nucleoside analogues provided durable suppression of plasma viral load in HIVinfected patients, with significant improvement in the CD4 cell count.

Sustained Efficacy of Nevirapine in Combination with Two Nucleoside Analogues in the Treatment of HIV-Infected Patients: A 48-Week Retrospective Multicenter Study

Background: Nevirapine, a nonnucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the durable suppression of HIV with nevirapine when used along with other nucleosides in HIV-infected patients who are treated in clinical practice needs further evaluation. Purpose: To evaluate the sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients in routine clinical practice. Design: A multicenter study from January 1997 to December 2000, with follow-up through 48 weeks, was conducted at four different genitourinary medicine clinics in the United Kingdom. Forty-four HIV-infected patients received nevirapine and two nucleoside analogues. Information from case notes regarding age, sex, side effects, viral load, and CD4 lymphocyte counts at baseline, 24 weeks, and 48 weeks was collected and analyzed. Virologic suppression, defined as HIV RNA concentration of less than 400 copies/mL at Weeks 24 and 48, was considered as the main outcome measure. Results: Out of 44 patients, 41 were men with a mean age of 39.3 years (95% CI 36.7-41.8). The baseline viral load was 2.11 × 102 to 9.74 × 105 copies/mL (median 7.7 × 104 and CD4 counts 6 to 605 cells/dL (M = 247; 95% CI 198-295). Of 39 patients who completed 48 weeks of treatment, viral load suppression was attained in 31 patients (79.4%; 95% CI 66.8-92.0) at 24 weeks and in 27 patients (69.2%; 95% CI 54-83) at 48 weeks. The CD4 lymphocyte count increased in 32 (82%) patients (mean 106 cells/dL, 95% CI 73-139, p = .0001, Wilcoxon signed rank test) after 24 weeks and in 33 (84.6%) patients (mean 160 cells/dL, 95% CI 115-204, p = .0001, Wilcoxon signed rank test) after 48 weeks of treatment. Of 20 patients whose baseline viral load was <100,000, 16 had viral load suppressed at 24 weeks and 15 at 48 weeks (p = .6, chi-square test). Conclusion: A regime of nevirapine with two nucleoside analogues provided durable suppression of plasma viral load in HIVinfected patients, with significant improvement in the CD4 cell count.

Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients.

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).

Ratio of two successive optical densities from the Roche HIV-1 monitor test as a measure of accuracy of estimates of human immunodeficiency virus RNA concentration.

In the Roche Amplicor HIV-1 Monitor Test, the ratio of the optical density used to estimate the RNA concentration and the optical density of the preceding or the following dilution can be used to identify specimens with inaccurate results which should be retested. We present an algorithm for the identification of such results.

Effects of HAART on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with haemophilia.

In multiply coinfected human immunodeficiency virus (HIV)-positive patients, we investigated the effects of high-activity antiretroviral therapy (HAART) using HIV protease inhibitors on three other viruses: hepatitis C virus (HCV), hepatitis G virus (HGV), and TT virus (TTV). Viral concentrations were measured serially by polymerase chain reaction methods in five patients with quadruple infection (HIV, HCV, HGV, and TTV) and in two patients with triple infection (HIV, HCV, and HGV) before and during HAART. In addition, CD4+ cell counts and serum alanine aminotransferase (ALT) levels were measured serially. Generally we observed no difference in serum HCV RNA, HGV RNA, or TTV DNA concentrations between samples obtained before and after initiation of HAART, whereas HIV RNA concentration decreased and CD4 counts increased in most patients. However, two patients had markedly decreased concentrations of HCV RNA and HGV RNA, respectively, more than 12 months after beginning HAART. Normalization of serum ALT levels was observed in a patient with decline of HCV RNA concentrations. No interactions were observed among these four viruses. HAART had no apparent direct effects on HCV, HGV, or TTV. Further studies will be required to elucidate whether the restoration of immune status through suppression of HIV replication by HAART may affect HCV or HGV RNA concentrations.

Trichomonas vaginalis as a cause of urethritis in Malawian men.

Trichomonas vaginalis is one of the most common sexually transmitted infections. In Malawi, rates of trichomoniasis in women are high. The prevalence of T. vaginalis infection in men is expected to be high but has not previously been documented. We sought to determine the prevalence of trichomoniasis in Malawian men with and without urethritis, to evaluate a polymerase chain reaction detection assay for T. vaginalis in urethral swabs and to examine the effect of T. vaginalis infection on excretion of human immunodeficiency virus (HIV) in semen. Men presenting at the Sexually Transmitted Diseases (STD) and Dermatology Clinics in Malawi were enrolled in a cross-sectional study. We compared a polymerase chain reaction-based test for T. vaginalis detection with wet-mount microscopy and culture of urethral swabs. HIV serology was determined by enzyme-linked immunosorbent assay (ELISA), and HIV-1 RNA concentrations in semen were measured by quantitative nucleic acid sequence-based analysis. T. vaginalis was detected in 51 of 293 men. The estimated prevalence among symptomatic men was 20.8% and among asymptomatic men, 12.2%. Polymerase chain reaction performed with a sensitivity of 0.82 (95% CI: 0.66-0.92) and specificity of 0.95 (95% CI: 0.91-0.97) compared to wet-mount microscopy and culture. There was no difference in the rate of HIV seropositivity in men with and without T. vaginalis infection. However, in men with symptomatic urethritis, the median HIV RNA concentration in seminal plasma from men with T. vaginalis was significantly higher that in seminal plasma from HIV-positive men without trichomonas.

A pilot study of combination therapy with indinavir, stavudine (d4T), and didanosine (ddI) in children infected with the human immunodeficiency virus

Twelve children infected with the human immunodeficiency virus were treated orally with indinavir, stavudine, plus didanosine for 12 to 48 weeks. Therapy was limited in some cases by nonadherence, intolerance, toxicity, and virologic failure. Marked increases in CD4+ lymphocyte counts and decreases in plasma human immunodeficiency virus RNA concentrations suggest that the regimen has potent antiviral activity. (J Pediatr 1998;132:543-6)

Combination Therapy With Stavudine and Didanosine in Children With Advanced Human Immunodeficiency Virus Infection: Pharmacokinetic Properties, Safety, and Immunologic and Virologic Effects

To obtain preliminary information on the pharmacokinetic properties, tolerance, safety, and antiviral activity of combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus (HIV) infection. Eight children (median age, 6.6 years; range, 2.8 to 12 years) with advanced HIV disease (median CD4 + lymphocyte count at baseline, 42 cells/ microL; range, 8 to 553 cells/microL) were treated with stavudine (2 mg/kg per day in two divided doses) and didanosine (180 mg/m2 per day in two divided doses) for 24 weeks. Seven children had histories of prior zidovudine therapy. All children had received stavudine alone for 19 to 33 months before the addition of didanosine to the treatment regimen. Children were assessed clinically and with laboratory studies at baseline, weekly through week 4 of combination therapy, and every 4 weeks thereafter. Analysis of stavudine and didanosine plasma half-life values, clearances, and area under the plasma concentration-versus-time curves revealed no obvious clinical pharmacokinetic interaction between the drugs through study week 12. Combination therapy was well tolerated, and there were no drug-associated clinical or laboratory adverse events. Signs and symptoms of peripheral neuropathy were not observed. All three children with baseline CD4 + lymphocyte counts greater than 50 cells/muL had greater than 20% increases in their counts within the first 12 weeks of therapy; CD4 + lymphocyte count increases were not observed in the other children. Plasma HIV RNA concentrations showed median declines of 0.88 log10 (range, -3.41 log10 to 0.31 log10) and 0.30 log10 (range, -0.63 log10 to 0.89 log10) at study weeks 12 and 24, respectively. Combination therapy with stavudine and didanosine was well tolerated and safe in this small group of children with advanced HIV disease. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. These findings should be confirmed, and the regimen's clinical efficacy should be examined, in controlled studies of HIV-infected children with less-advanced disease.