Viral Load

To analyze the clinical efficacy of cidofovir combined with highly active anti-retroviral therapy (HAART) in AIDS-related progressive multifocal leukoen-cepalopathy (PML), a multicenter observational study was performed. Consecutive HIV-positive patients with histologically or virologically proven PML and at least 4 weeks of treatment after diagnosis were examined: 27 patients were treated with HAART, whereas 16 patients were treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and every other week thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR. Baseline virologic, immunologic, and clinical characteristics as well as HIV RNA and CD4 responses to HAART were homogeneous between the groups. The median follow-up was 132 weeks. In one case (6%), cidofovir was permanently discontinued because of severe proteinuria. One-year cumulative probability of survival was 0.61 with cidofovir and 0.29 without (log rank test P = 0.02). After adjusting for baseline CD4 counts, JC viral load in CSF, Karnofsky, and use of HAART prior to the onset of PML, the use of cidofovir was independently associated with a reduced risk of death (hazard ratio, 0.21, 95% confidence interval, 0.07–0.65; P = 0.005). A randomized study will definitively establish whether cidofovir confers significant advantage over HAART alone in AIDS-related PML.

Hepatitis C virus (HCV) is not directly cytopathic to the hepatocytes; however, host immune response against the virus does cause hepatic injury. Production of the HCV antibody is a host immune response to a viral antigen. The currently used HCV antibody assay is a qualitative, not quantitative, assessment. In this study, we sought to quantitatively estimate HCV antibody levels in patients who had undergone liver transplantations at the University of Rochester Medical Center, Rochester, New York, and correlate these levels with HCV RNA viral load, genotype, severity of recurrence, and anti-HCV treatment. From 39 liver transplantation patients, we obtained 141 blood samples for quantitative HCV RNA to measure HCV antibody levels quantitatively. Most antibody levels were within a narrow range with a mean of 32.9+/-5.1. Samples with undetectable RNA had a mean antibody level of 31.4+/-8.0, and samples with a positive RNA had mean level of 33.0+/-4.6. The mean antibody levels were signi...

Prevalence and factors associated with sexual dysfunction in HIV-positive women are poorly known. This was a cross-sectional study in a cohort of HIV-infected women. Clinically stable women were invited to participate in a female sexual dysfunction (FSD) evaluation with Female Sexual Function Index (FSFI) exploring desire, arousal, lubrication, orgasm, pain and satisfaction. An FSFI score <23 was used for defining FSD. Variables evaluated included body appearance satisfaction, interference of body changes with habits, social life and attitudinal aspects of body image, health-related quality of life, hormonal assessment, menopause, cumulative exposure to antiretroviral drug classes and immune-virological parameters. Lipodystrophy was defined according to the HIV Outpatient Study definition. A total of 185 women completed the FSFI. The mean (+/-SD) age was 42 years (+/-5), 27% had CDC stage C, the mean (+/-SD) CD4+ T-cell count was 508 cells/microl (+/-251) and median HIV RNA was 1...

We attempted to define optimal conditions for amplification of low copy number HIV-1 RNA sequences in plasma samples, applying improved conditions for nucleic acid extraction and amplification. Several methodologic parameters were evaluated, including methods of RNA extraction, volumes of plasma samples, proportion of extracted RNA used as a template for amplification, and reverse transcriptase-DNA polymerase enzyme combination employed in cDNA synthesis and polymerase chain reaction amplification. With this improved assay, we were able to obtain sufficient amounts of amplified material for direct sequencing in 97% of all plasma samples in our study, including 88% of samples with viral loads <80 copies/mL, 78% of samples with viral loads <50 copies/mL, and even 2 (67%) of 3 samples with <20 copies/mL. This procedure could be useful for testing resistance mutations in patients undergoing highly active antiretroviral therapy, in which the viral load is commonly <400 copies...

There are few data on plasma and intracellular pharmacokinetics (PK) of once-daily (q24h) nucleoside analogues in HIV-infected children. Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q12h) were included in this single-arm, open-label, crossover study. Intensive plasma PK sampling was performed at steady state, after which children switched to q24h dosing and PK sampling was repeated 4 weeks later. Daily area under the curve (AUC0-24) and peak level (Cmax) of q24h and q12h regimens were compared by geometric mean ratios (GMRs) with 90% confidence intervals (CIs). Children were followed for 24 weeks to evaluate safety and virological response. 24 children were enrolled, of whom 20 [median age (range) 5.6 (2.1-12.8) years] had evaluable PK data for 3TC (n=19) and/or ABC (n=14). GMRs of 3TC and ABC AUC0-24 and Cmax q24h versus q12h significantly exceeded 1.0. GMRs were not significantly differe...

Psychosocial factors may directly impact HIV health measures such as viral load (VL) whether or not patients are taking antiretroviral treatment (ART) consistently. Structural equation modeling plus Baron and Kenny's (1986) four-step approach were used to test a mediated model predicting VL among 246 HIV-infected adults who were on ART. Exogenous variables were social support, barriers to adherence, and stress. Moderators were alcohol use, marijuana use, and neurocognitive impairment. A small positive association between marijuana use and ART adherence approached significance. Only barriers to adherence predicted a decrease in adherence rates and an increase in VL. No other factors were significantly associated with either VL or adherence, and no interaction effects between exogenous variables and moderators were identified. The association between barriers to adherence and VL was partially mediated by ART adherence. Findings provide modest support for a direct link between psyc...

In a double-blind, phase 3 trial, 663 HIV-infected, virologically suppressed adults were randomized to switch to tenofovir alafenamide (TAF; n=333) vs. remain on tenofovir disoproxil fumarate (TDF; n=330), each coformulated with emtricitabine (FTC), while continuing their third agent (boosted protease inhibitor or unboosted third agent). At week 96, 88.6% on FTC/TAF and 89.1% on FTC/TDF had HIV-1 RNA <50 copies/mL (adjusted difference -0.5%; 95%CI [-5.3%, 4.4%]). Proteinuria, albuminuria, proximal renal tubular function, and bone mineral density improved after switching to TAF- from TDF-containing regimens. These longer-term data support FTC/TAF as a safe, well tolerated, and durable nucleotide reverse transcriptase inhibitor backbone.

Assessing treatment efficacy and early infant diagnosis (EID) are critical issues in HIV disease management. Point-of-care assays may greatly increase the possibility to access laboratory monitoring also in rural areas. Recently two new laboratory tests have been developed by Cepheid (Sunnyvale, California) the Xpert HIV-1 Viral Load for viral load determination and the Xpert HIV-1 Qualitative for early infant diagnosis. We conducted a study in Blantyre, Malawi, comparing the 2 methods versus the Abbott real time quantitative and qualitative assays, for viral load and EID respectively. We tested 300 plasma samples for viral load determination and 200 samples for infant diagnosis. HIV-1 RNA values of the 274 samples quantified by both assays were highly correlated (Pearson r=0.95, R(2)=0.90). In 90.9% of the cases the two methods were concordant in defining the HIV-1 RNA levels as detectable or undetectable. For EID, the Xpert HIV-1 Qualitative assay yielded the same identical results as the Abbott assay. Both the quantitative and the qualitative Xpert assays are promising tools to monitor treatment efficacy in HIV patients receiving treatment and for early diagnosis in HIV-exposed infants.

ObjectiveTo assess the risk factors associated with heterosexual HIV transmission among South Indian discordant couples enrolled in clinical care.To assess the risk factors associated with heterosexual HIV transmission among South Indian discordant couples enrolled in clinical care.MethodsA nested matched case–control study of serodiscordant couples in which the HIV-infected partner (index case) was enrolled in care. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV-1 RNA loads were measured at enrolment and longitudinally over 12 months of follow-up. The study included 70 cases who seroconverted during study follow-up and 167 matched controls who remained persistently serodiscordant.A nested matched case–control study of serodiscordant couples in which the HIV-infected partner (index case) was enrolled in care. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV-1 RNA loads were measured at enrolment and longitudinally over 12 months of follow-up. The study included 70 cases who seroconverted during study follow-up and 167 matched controls who remained persistently serodiscordant.ResultsThe incidence of HIV infection among the initially seronegative partners was 6.52 per 100 person-years. Persistently discordant patients were more likely to have initiated highly active antiretroviral therapy (HAART) than patients in seroconverting relationships (62.9%vs. 42.9%) (P=0.001). Patients in seroconverting relationships had significantly higher plasma viral loads (PVLs) than patients in discordant relationships at enrolment, at 6 months and at 12 months (P<0.05). Patients in seroconverting relationships were less likely to use condoms with their primary partners than patients in discordant relationships (P<0.05). Patients in relationships that seroconverted between 6 and 12 months were diagnosed more often with genital Herpes simplex than patients in discordant relationships (P=0.001). In the univariate and multivariate logistic regression, the following variables were associated with seroconversion: PVL >100 000 [odds ratio (OR): 1.82; 95% confidence interval (CI): 1.1–2.8], non-disclosure of HIV status (OR: 5.5; 95% CI: 4.3–6.2) and not using condoms (OR: 2.8; 95% CI: 2.4–3.6).The incidence of HIV infection among the initially seronegative partners was 6.52 per 100 person-years. Persistently discordant patients were more likely to have initiated highly active antiretroviral therapy (HAART) than patients in seroconverting relationships (62.9%vs. 42.9%) (P=0.001). Patients in seroconverting relationships had significantly higher plasma viral loads (PVLs) than patients in discordant relationships at enrolment, at 6 months and at 12 months (P<0.05). Patients in seroconverting relationships were less likely to use condoms with their primary partners than patients in discordant relationships (P<0.05). Patients in relationships that seroconverted between 6 and 12 months were diagnosed more often with genital Herpes simplex than patients in discordant relationships (P=0.001). In the univariate and multivariate logistic regression, the following variables were associated with seroconversion: PVL >100 000 [odds ratio (OR): 1.82; 95% confidence interval (CI): 1.1–2.8], non-disclosure of HIV status (OR: 5.5; 95% CI: 4.3–6.2) and not using condoms (OR: 2.8; 95% CI: 2.4–3.6).ConclusionsCouples-based intervention models are crucial in preventing HIV transmission to seronegative spouses. Providing early treatment for sexually transmitted infections, HAART and enhancing condom use and disclosure could potentially decrease the risk of HIV transmission within Indian married couples.Couples-based intervention models are crucial in preventing HIV transmission to seronegative spouses. Providing early treatment for sexually transmitted infections, HAART and enhancing condom use and disclosure could potentially decrease the risk of HIV transmission within Indian married couples.