Plasma HIV Viral Load Research Articles

Pulmonary Kaposi sarcoma in the era of highly active antiretroviral therapy

Since the introduction of highly active antiretroviral therapy (HAART) there has been a dramatic reduction in the incidence of Kaposi sarcoma (KS) and an improvement in survival. We wished to examine whether the outcome in pulmonary KS (pKS) has also altered. In a single-institution cohort of 1140 HIV-positive patients with KS, 305 patients were diagnosed in the HAART era (1996-2004). We examined the clinicopathological features and outcomes of these patients, of whom 25 had pKS and 280 did not. Patients with pKS had lower CD4 cell counts at the time of KS diagnosis (Mann-Whitney U-test P=0.005). The incidence of pKS was higher in African patients than in non-African patients in this sample (Fisher's test, P=0.001). There were no significant differences in age, gender, plasma HIV-1 viral load or prior HAART treatment at the time of KS diagnosis. Five-year overall survival in the pKS group was 49% [95% confidence interval (CI) 26-73%] as compared with 82% (95% CI 76-87%) for the non-pKS group (log rank, P<0.0001). PKS remains an ominous diagnosis in the era of HAART, with a median survival of just 1.6 years.

Human Papillomavirus (HPV) Detection Among Human Immunodeficiency Virus–Infected Pregnant Thai Women: Implications for Future HPV Immunization

Human immunodeficiency virus (HIV)-infected women are at increased risk for developing cervical cancer and for infection with human papillomavirus (HPV). Prophylactic vaccines targeting HPV types 16 and 18 are being evaluated for efficacy among young women. The goal was to assess the prevalence of HPV among HIV-infected pregnant women in Bangkok and to evaluate the need for prophylactic HPV vaccines studies in this population. The study population consisted of 256 HIV-infected pregnant women who participated in a mother-to-child HIV transmission trial. Stored cervicovaginal lavage samples were tested for the presence of HPV DNA by polymerase chain reaction with PGMY09/11 primers and reverse line-blot hybridization for determination of anogenital HPV types. HPV prevalence was 35.5% (91/256); high-risk HPV prevalence was 23.4% (60/256). HPV type 16 or 18 was present in 8.2% (21/256). Almost half of all infections were multiple. Furthermore, overall HPV detection was associated with abnormal cervical cytology (P<0.001) and higher HIV-plasma viral load (P=0.007). Only one-quarter of HIV-infected pregnant women in Bangkok had high-risk HPV types; less than 10% had HPV types 16 or 18. As the HPV prevalence is expected to increase during HIV disease, prophylactic vaccines targeting HPV types 16 and 18 should be studied among HIV-infected women not yet infected with these HPV types and not previously exposed.

Thymic volume, T-cell populations, and parameters of thymopoiesis in adolescent and adult survivors of HIV infection acquired in infancy

Antiretroviral therapy has significantly prolonged the lifespan of children who acquire HIV infection in infancy, but the impact of HIV on thymus-mediated maintenance of T lymphocytes has not been studied. To examine the long-term effects of HIV infection in childhood on thymopoiesis, thymic volume and parameters of thymic function from clinically stable adolescents and young adults with HIV infection acquired in infancy were compared with those from uninfected controls. Thymic volume was determined using three-dimensional reconstruction and volumetric analysis of non-contrast enhanced computed tomography images of the upper chest. The degree of fat involution was assessed using a semiquantitive scoring system. CD4 and CD8 T cell populations and T cell receptor recombination excision circles (TREC) concentrations in peripheral blood lymphocytes were measured in all subjects. Twenty youths (aged 17.6 +/- 2.5 years) with HIV infection acquired perinatally (n = 18) or by neonatal transfusion (n = 2) were enrolled whose HIV plasma viral load had been undetectable for a median of 3.1 years, along with 18 seronegative healthy young adults (aged 20.6 +/- 1.3 years). HIV infected subjects and controls had indistinguishable CD4 T cell counts, thymus volumes (20.5 versus 15.8 cm), thymic index scores, and TREC values. Thymic volume correlated with the number and percentage of CD4 T lymphocytes in the control group and with the number of TREC in CD4 lymphocytes in the HIV infected group. Long term survivors of pediatric HIV infection appear to have retained or recovered thymic volume and thymic activity approximating uninfected youths.

Absence of seroreversion in 80 HAART-treated HIV-1 seropositive patients with at least five-years undetectable plasma HIV-1 viral load

Partial or complete seroreversion for HIV-1, or incomplete antibody evolution are relatively rare events that have so far only been described in patients treated with HAART early after virus infection. Whether seroreversion is seen in patients treated effectively with HAART years after their acute infection has not been investigated so far. Therefore we have investigated anti-HIV antibody levels in 80 patients treated with HAART during chronic HIV-1 infection, who had an undetectable HIV-1 plasma viral load for at least five years. In none of the patients we observed seroreversion, and there was also no significant decrease or increase in antibody levels in this group of patients. So, successful HAART treatment during chronic HIV-1 infection does not induce seroreversion.

Prognostic value of HIV-1 Gag-specific CD4+ T-cell responses for progression to AIDS analyzed in a prospective cohort study

The causal relationship between HIV-specific CD4+ T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4+ T cells were analyzed in long-term asymptomatic individuals (LTA; n = 6) and progressors to AIDS (n = 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4+ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gag-specific CD4+ T cells producing IL-2 or IFNgamma were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2+, IFNgamma+, or IL-2+IFNgamma+ CD4+ T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4+ T-cell responses, rather than HIV-specific CD4+ T-cell responses controlling HIV plasma viral load.

Association of genital shedding of herpes simplex virus type 2 and HIV-1 among sex workers in rural Zimbabwe

Herpes simplex virus type 2 (HSV-2) facilitates sexual acquisition of HIV-1 but data on transmission are less clear. In this study the interaction between genital shedding of HIV-1 and HSV-2 was explored among Zimbabwean sex workers. Women (n = 214) were interviewed about genital symptoms. Blood samples were analysed for HIV-1 and HSV-2 antibodies, HIV-1 plasma viral load (PVL) and CD4 lymphocyte count and genital swabs for detection of HIV-1 and HSV-2 genital shedding, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis, and a cervico-vaginal lavage (CVL) for quantitative measurement of HIV-1 shedding. Shedding analyses were undertaken on women co-infected with HSV-2 and HIV-1. A total of 124 women were co-infected with HIV-1 and HSV-2; 58 were infected with HSV-2 alone. Most HIV-1-infected women were co-infected with HSV-2 (95.4%). Genital HIV-1 shedding was detected in 84.3% of co-infected women and was associated with low CD4 cell count and high PVL but not with reported symptoms of genital herpes or genital shedding of HSV-2. There was no difference in HIV-1 shedding among women shedding HSV-2 (79.3%) and women not shedding HSV-2 (83.2%) (P = 0.64). The adjusted odds ratio for HIV-1 shedding between HSV-2 shedders and non-shedders was 0.8 [95% confidence interval (CI), 0.2-3.3]. HIV-1 PVL(log10) and CVL viral load(log10) were correlated (r = 0.38; 95%CI, 0.2-0.5). After adjusting for PVL, genital symptoms and age, HSV-2 shedding had no effect on CVL viral load (P = 0.13). Rate and quantity of HIV-1 genital shedding do not appear to be altered by presence of HSV-2 genital shedding.

Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda

The impact of antiretroviral therapy (ART) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown. To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART. A prospective cohort study was performed in rural Uganda. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling, voluntary counseling and testing (VCT) for cohabitating partners and condom provision. At baseline and follow-up, participants' HIV plasma viral load and partner-specific sexual behaviors were assessed. Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months. The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated, based on established viral load-specific transmission rates. Six months after initiating ART, risky sexual behavior reduced by 70% [adjusted risk ratio, 0.3; 95% confidence interval (CI), 0.2-0.7; P = 0.0017]. Over 85% of risky sexual acts occurred within married couples. At baseline, median viral load among those reporting risky sex was 122 500 copies/ml, and at follow-up, < 50 copies/ml. Estimated risk of HIV transmission from cohort members declined by 98%, from 45.7 to 0.9 per 1000 person years. Providing ART, prevention counseling, and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ugandan adults during the first 6 months of therapy. Integrated ART and prevention programs may reduce HIV transmission in Africa.

Fluorogenic LUX Primer for Quantitation of HIV-1 by Real-Time RT-PCR

Measurement of HIV-1 viral load in plasma is an important marker of disease progression and efficacy of antiretroviral therapy. Real-time polymerase chain reaction (PCR) offers an opportunity to develop more affordable alternative viral load assays. This article reports on the development of a novel real-time reverse-transcriptase (RT)-PCR assay for quantitation of HIV-1 RNA copies. This assay utilizes the LightCycler (version 2) real-time PCR platform and light upon extension (LUX) primer for specific detection of amplicons. An external standard (ES) for quantitation of viral RNA represents an in vitro transcribed RNA. The LUX assay shows a wide linear (R2 = 0.99) dynamic range from 4 x 10(6) to 4 x 10(2) copies/mL. Analytical sensitivity of the assay is 4 x 10(2) copies/mL of ES RNA. Intra- and inter-assay variability of the LUX assay was less than 0.5log(10) copies of ES RNA (i.e., no clinically significant variability was found). Virology quality assurance (VQA) HIV-1 RNA copy controls were used to validate ES and preliminarily evaluate the assay performance. This feasibility study demonstrated that the LUX assay is sensitive, reproducible, and compares well to the Roche Amplicor tests used for characterization of the RNA copy controls. These results suggest further evaluation of the LUX assay using a large cohort of well-characterized samples from HIV-1 positive individuals.

Is the plasma HIV-1 viral load an accurate predictor of genital tract viral load in pregnancy?

Since the benefit of cesarean delivery with a viral load <1,000 copies/mL is unknown, our objective was to quantitate HIV-1 RNA in the genital tract of HIV infected pregnant women and to determine if this correlated with plasma viral load (VL).

Management of end stage liver disease (ESLD): What is the current role of orthotopic liver transplantation (OLT)?

Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

Photopheresis in HIV-1 Infected Patients (pt) Using Benzoporphyrin Derivative (BPD-MA) Induces Apoptosis in CD4 Cells, Increases Intracellular Expression of Chemokines and Decreases HIV Infectivity and Viral Load.

HIV is able to elude both cellular and humoral arms of the immune system; thereby making viral control difficult. Extra corporeal photochemotherapy (ECP) or photopheresis is an immunomodulatory therapy in which lymphocytes are reinfused into the host after exposure to a photoactive compound and ultraviolet A light. It is an effective therapeutic approach to several disorders of the immune system including acute and chronic graft-versus-host disease, scleroderma, and cutaneous T-cell lymphoma. This process may offer a novel approach to viral control with minimal or no toxicity. We initiated an ex vivo and subsequently a clinical pilot trial utilizing Benzoporphyrin Derivative as the photosensitive compound. Ex vivo dosing studies identified the minimum energy levels of light exposure and concentrations of BPD that eradicated both cell-free and cell-associated HIV-1 infectivity without destroying the virus particles or infected leukocytes. Leukocytes so treated remained viable. They did demonstrate altered cytokine and chemokine expression with apoptosis induced in a minority of CD4 but not CD8 positive cells. A pilot in vivo, 24 week clinical trial in seven HIV-1 infected patients (all were required, upon entry, to have viral loads of > 10,000) using the photopheresis parameters established above demonstrated that the treatment was well tolerated and beneficial. Three individuals who had rapidly rising viral loads prior to initiating therapy stabilized once treatment began. Two of which had a (sustained) greater than .5 log decrement and 5 had stable plasma viral loads (less than a .5 log increment or decrement) with varied effects on absolute CD4 and CD8 positive lymphocytes counts. One subject achieved a greater than 1 log decrement in HIV-1 plasma viral load also developed undetectable in vivo cell-free and cell-associated HIV-1 infectivity while demonstrating an increased in vitro lymphocyte mitogen stimulation index. Subsequently, under amended and successor protocol 5 additional 12 month courses were administered to three additional patients and two of the previous enrollees. The area under the curve for viral load (viral load x # of weeks) for these twelve courses of therapy showed a significant decrease from pre to post therapy (p 0.007). There were no significant changes in CD4 or CD8 numbers area under the curve (CD4 number # of weeks and CD8 number x # of weeks). None of the subjects developed an AIDS defining illness during the course of therapy nor were there any treatment associated toxicities. These studies suggest that ECP augments activity of various arms of the immune system without any significant toxicity and may be effective in controlling HIV replication. We have now instituted a randomized Phase II study utilizing long-term photopheresis (twice monthly for 48 weeks) in addition to anti-retroviral therapy versus anti-retroviral therapy alone to further determine efficacy and mechanism of activity.

Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial

Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence. We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol. The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001). Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea. Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.

IL-7 as a potential therapy for HIV-1-infected individuals

Highly active antiretroviral therapy (HAART), although effective in ameliorating the quality of life of HIV-1-infected individuals and their survival, has not been able to eradicate HIV-1. In fact, when HAART is interrupted, HIV-1 plasma viral load rebounds from viral reservoirs such as resting CD4+ T lymphocytes, monocytes and macrophages, remaining a major obstacle in attempting HIV eradication. Different therapeutic strategies have been attempted, such as structured treatment interruption (STI), immunotherapy (interleukin [IL]-2 and anti-CD3 antibodies [e.g., OKT3]), to try to stimulate HIV-1 out of latency along with antiretroviral intensification therapy. IL-7, a pleiotropic cytokine, bears diverse immune properties and plays a major role in T cell homeostasis. Moreover, IL-7 has recently been investigated as a possible immune adjuvant as well as a viral strain-specific inducer of HIV-1 replication. In fact, IL-7 was shown not only to be more effective than IL-2 in stimulating HIV-1 replication from resting CD4+ T lymphocytes ex vivo, but also to selectively induce a specific HIV-1 viral strain as compared with IL-2, suggesting the potential need for different viral inducers if complete eradication is to be achieved. In this present review, different immunological and virological properties of IL-7 are discussed, along with the possibility of its use as part of a combined antiretroviral-immune rationally based HIV-1 eradication approach.

Role of Lymphocyte Multidrug Resistance Protein 1 in HIV Infection

The multidrug resistance protein 1 (MRP1) is a drug transporter that protects cells from oxidative stress, which increases HIV-1 replication. The aim of this study was to characterize the expression, function, and role of lymphocyte MRP1 in HIV-1 infection and its modulation by antiretroviral drugs such as the protease inhibitors (PIs). Peripheral blood mononuclear cells (PBMCs) from HIV-positive individuals do not show significant alterations of MRP1 expression despite highly active antiretroviral therapy and HIV plasma viral load levels; however, they exhibit different intracellular MRP1 expression as compared with healthy subjects. By contrast, MRP efflux function is increased in subjects with primary HIV infection and becomes defective in later stages of the infection. PI- and probenecid (PBCD)-mediated inhibition of MRP lowers the in vitro stress-induced response of lymphoid cells by reducing the level of the specific reactive oxygen species superoxide anion and hydrogen peroxide. Finally, the blockade of MRP by PBCD and PIs down-modulates HIV-1 replication by a mechanism independent of inhibition of the HIV-1 protease. Our results are consistent with a model wherein HIV replication is favored by the MRP1-related oxidative stress and inhibition of MRP1 may contribute to the antiviral activity of PIs.

Triple nucleoside reverse transcriptase inhibitor‐ vs. nonnucleoside reverse transcriptase inhibitor‐containing regimens as first‐line therapy: efficacy and durability in a prospective cohort of French HIV‐infected patients

Based on the short-term results of the AIDS Clinical Trials Group (ACTG) A5095 trial, zidovudine (ZDV)/lamivudine (3TC)/abacavir (ABC) is no longer recommended as a first-line antiretroviral regimen. Data on the efficacy of this triple nucleoside reverse transcriptase inhibitor (NRTI) combination compared with the gold-standard nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen could provide important information. Patients were selected from three prospective cohorts of patients who received first-line therapy with ZDV/3TC plus an NNRTI or ABC, started after January 1998. Immunovirological changes and the proportion of treatment discontinuations were compared between groups. Of the 380 patients, 190 started on ABC [the triple-NRTI group (3N)] and 190 on NNRTI. At baseline, there was no statistical difference between the NNRTI and 3N groups for age (mean=38 years), sex (66% male) or CD4 cell count (mean=305 cells/muL). Mean baseline plasma HIV-1 viral load (pVL) was higher in the 3N group (4.6 vs. 4.3 log10 HIV-1 RNA copies/mL: P<0.01). Lower and higher estimates of median pVL decrease at month 24 were 2.05 and 4.76 log10 copies/mL in the 3N group, and 1.73 and 4.31 log10 copies/mL in the NNRTI group (not significant). CD4 cell count evolution did not differ between groups. Treatment discontinuation occurred in 45% vs. 44% of patients in the NNRTI and 3N groups, respectively, after median durations of 9 and 4 months, respectively (P=0.02). In this prospective cohort, 3N and NNRTI regimens as first-line therapy produced similar immunovirological responses.

Incidence of and Risk Factors for Clinically Significant Methicillin-Resistant Staphylococcus aureus Infection in a Cohort of HIV-Infected Adults

Outbreaks of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) have been noted in multiple sites in the United States. This study's purpose was to estimate trends in the incidence of and risk factors for clinically significant MRSA (CS-MRSA) infection in a cohort of HIV-infected adults. A retrospective clinic-based cohort (January 1, 2000-December 31, 2003) study. We ascertained all initial episodes of CS-MRSA and categorized them by primary site. Incidence rates were estimated by half year. Risk factors for CA-MRSA infection were identified using Cox modeling. Of 126 potential events, 94 were CS. Their primary sources were 83% skin or soft tissue, 10% blood, 6% respiratory, and 1.0% other sites. Among these, 60% were CA and 40% were nosocomial. Of antibiotics tested, only cotrimoxazole resistance was associated with nosocomial acquisition. The 3455 patients contributed 7003 person-years at risk. The incidence of CS-MRSA infection increased 6.2-fold from the first to the last half year. In multivariate analysis, independent predictors of CA-MRSA infection included HIV transmission by men who have sex with men or by injection drug use, CD4 count <50 cells/muL, log10 HIV plasma viral load, and absence of cotrimoxazole prophylaxis. The incidence of initial CS-MRSA events increased more than 6-fold in a 4-year period. The associations between CA-MRSA infection and HIV severity indicators merit examination in other cohorts.

Dynamics of monocyte chemoattractant protein type one (MCP-1) and HIV viral load in human cerebrospinal fluid and plasma

Background Increased expression of monocyte chemoattractant protein type 1 (MCP-1) is associated with HIV CNS disease. This study evaluated the temporal relationships between MCP-1 expression and HIV replication in the CNS. Methods MCP-1 and HIV viral load (VL) were measured in serially obtained samples of plasma and cerebrospinal fluid (CSF) in subjects either interrupting (TI) or starting (TS) antiretroviral therapy. Results Following TI, plasma VL rebounded first, followed by increases in CSF MCP-1, which immediately preceded or coincided with a rebound of CSF VL. Conclusion The close temporal relationship of the increase of MCP-1 and CSF VL suggests that they are co-regulated, or that one is a stimulus for the other.

Genital HIV-1 viral load is correlated with blood plasma HIV-1 viral load in Brazilian women and is reduced by antiretroviral therapy

Cervicovaginal secretions represent the primary vehicle in mother to infant and sexual HIV-1 transmission. Understanding the viral dynamics in this compartment is important to improve interventions to decrease HIV transmission. To evaluate the correlation of HIV-1 blood plasma viral load and cervicovaginal HIV-1 viral load and the effect of antiretroviral therapy (ART) on cervicovaginal HIV-1 viral load. A cross-sectional study among HIV-1 infected women recruited between February 2002 and January 2003 and a longitudinal study that included 11 women who initiated ART were performed. HIV-1 viral load was measured in the female genital tract and in blood plasma using the Nuclisens assay before and 1 month after ART introduction. HIV-1 viral load in cervicovaginal lavage was significantly correlated with HIV-1 blood plasma viral load (n = 27, Spearman rho = 0.73, p<0.001). In the longitudinal study, antiretroviral therapy was associated with a reduction of 1.44 log10 on genital HIV-1 viral load (95% CI = 0.57-2.30, p = 0.004, Student's t-test). HIV-1 viral load in female genital secretions is correlated with blood plasma HIV-1 viral load. Antiretroviral therapy substantially reduces HIV-1 viral load in the female genital tract.

Cryoglobulinemia in subjects with HCV infection alone, HIV infection and HCV/HIV coinfection

To assess the prevalence of cryoglobulinemia in three groups of patients: HCV-positive/HIV-negative, HCV/HIV co-infected and HIV mono-infected. From September 2002 to December 2003, 58 patients with documented HCV infection, 70 subjects with HIV/HCV co-infection, and 48 subjects with HIV infection alone were enrolled. Serum samples were tested for detectable cryoglobulins, liver enzymes, HCV viral load and HCV genotypes. Plasma HIV-RNA levels and CD4+ cell count were also evaluated in HIV-positive subjects. Cryoglobulinemia was detected in 24.1% HCV mono-infected, 14.2% HCV/HIV co-infected and 6% HIV mono-infected patients. A significant statistical correlation was found between the presence of cryoglobulins and HCV infection (P = 0.03), while cryoglobulins were unrelated to HIV mono-infection (P = 0.16) and HCV/HIV co-infection (P=0.7). No significant correlation was observed between the presence of cryoglobulinemia and alanine transaminase (ALT) levels, HCV viremia and duration of HCV infection. Circulating cryoglobulins in HIV patients were not correlated with plasma HIV viral load, CD4+ cell count or duration of HIV infection. Only two HCV mono-infected patients complained of arthralgia. A similar rate of cryoglobulinemia prevalence was detected in the patient groups with an HCV-related infection. HIV infection does not appear to play a significant role in cryoglobulin production.

The Safety of Discontinuation of Maintenance Therapy for Cytomegalovirus (CMV) Retinitis and Incidence of Immune Recovery Uveitis Following Potent Antiretroviral Therapy

Background: Reconstitution of immune function during potent antiretroviral therapy can prompt discontinuation of maintenance cytomegalovirus (CMV) therapy but has also been associated with sight-threatening inflammatory conditions including immune recovery uveitis (IRU). Method: Patients with inactive CMV retinitis and a CD4+ cell count above 100/mm3, receiving CMV therapy and stable combination antiretroviral therapy, were assigned to one of two groups based on willingness to discontinue CMV therapy. Results: Thirty-eight participants were enrolled: 28 discontinued anti-CMV therapy (Group 1) and 10 continued CMV treatment (Group 2). Median on-study follow-up was 16 months. One Group 1 participant who experienced an increase in plasma HIV viral load and a decline in CD4+ cell count developed confirmed progression of CMV retinitis. Progression or reactivation CMV retinitis was not observed among Group 2. IRU was present at study entry in 3 participants. Six participants in Group 1 and 3 participants in Group 2 developed IRU on-study. CMV viremia was not detected in any participants, and urinary shedding of CMV was intermittent. Conclusion: Recurrence of CMV retinitis following discontinuation of anti-CMV therapy among patients with antiretroviral-induced increases in CD4+ cell count was rare. However, IRU was common in both those who maintained and discontinued anti-CMV therapy.