Higher HIV-1 RNA Levels Research Articles

Abacavir/Lamivudine Fixed Dose Combination in the Treatment of Patients with HIV Infection

HIV infection remains a common cause of morbidity and mortality worldwide. Fortunately, patients treated with combination antiretroviral therapy (ART) have significantly improved survival rates and quality of life. The standard of care for the treatment of ART-naive patients includes three drugs, two of which should be nucleoside reverse transcriptase inhibitors (NRTIs). Abacavir/lamivudine (ABC/3TC) is a fixed dose combination NRTI tablet that has been approved as an NRTI backbone. ABC/3TC is among the NRTI combinations that are recommended as first line in the most recent International AIDS Society–USA guidelines and WHO European Region protocol. However, owing to recently published data raising the possibility of an association between abacavir and heart disease, as well as data regarding efficacy in patients with higher HIV RNA levels, ABC/3TC has now been listed as an alternative NRTI backbone in the latest USA Department of Health and Human Services guidelines. While ABC has been associated with a hypersensitivity reaction that may be severe, a new test has been demonstrated to be effective in screening for the gene that is associated with this reaction.

The Effect of Mental Illness, Substance Use, and Treatment for Depression on the Initiation of Highly Active Antiretroviral Therapy among HIV-Infected Individuals

Information regarding the prevalence of mental illness and substance use among HIV-infected patients and the effect of these problems on HIV treatment is needed. We conducted an observational study of patients in the University of Washington (UW) HIV Cohort to determine prevalence rates for mental illness and substance use. Cox regression analyses were used to examine the relationship between mental illness and substance use, pharmacologic treatment for depression/anxiety, and initiation of highly active antiretroviral therapy (HAART) within 9 months of becoming eligible for HAART. Among 1774 patients in the UW HIV cohort during 2004, 63% had a mental illness (including mood, anxiety, psychotic, or personality disorders), 45% had a substance use disorder, and 38% had both. There were 278 patients who met criteria for HAART eligibility. After controlling for other factors, patients with depression and/or anxiety were significantly less likely to initiate HAART compared with patients without a mental illness (hazard ratio [HR] 0.4, p = 0.02). However, patients with depression/anxiety who received antidepressant/antianxiety medications were equally likely to initiate HAART as patients without a mental illness (HR 0.9, p = 0.5). We found that patients with mental illness or substance use disorders receive HAART at lower CD4+ cell counts and higher HIV-1 RNA levels than patients without these disorders. However, HAART initiation among patients who receive treatment for depression/anxiety is associated with no delay. Screening for these disorders in primary care settings and access to appropriate treatment are increasingly important components of providing care to HIV-infected patients.

Smoking and predictors of pneumonia among HIV-infected patients receiving care in the HAART era.

Background: Smoking tobacco is disproportionably common among HIV-infected patients in the highly active antiretroviral therapy (HAART) era. Methods: An observational cohort study of 300 HIV-positive patients receiving care between 1996 and 2005 examined the effect of smoking on pneumonia risk. Multivariable analyses assessed the association between smoking and pneumonia risk and identified independent predictors of pneumonia during the HAART era. Results: Current smoking was common (67%). Eighty-two patients (27%) experienced 119 pneumonia episodes during 2151 patient-years of follow-up, with 7.2 episodes/100 person-years among smokers and 2.9 episodes/100 person-years among non-smokers (unadjusted incidence rate ratio (IRR): 2.50 (95% CI: 1.58, 4.09). Adjustment for age and HIV RNA level resulted in an IRR of 1.77 (95% CI: 0.98, 3.21). No prior antiretroviral therapy use (P-value <0.001), higher HIV RNA level (P-value = 0.01), lower CD4 count (P-value = 0.01), younger age (P-value = 0.01), and alcohol use (P-value = 0.04) were independent predictors of pneumonia. HAART use decreased pneumonia risk (IRR 0.28, 95% CI: 0.18, 0.44). Conclusions: While HIV-positive smokers had over a 2-fold increase in the rate of pneumonia, the trend did not reach statistical significance in multivariable models. Clinical factors such as HAART, alcohol use and immunological status are important in pneumonia risk.

Observational Study on HIV-Infected Subjects Failing HAART Receiving Tenofovir Plus Didanosine as NRTI Backbone

We evaluated the efficacy of tenofovir (TDF) - and didanosine (ddI)-containing backbones in HIV-infected experienced subjects. We included in the study 245 subjects who started a TDF/ddI-containing HAART with HIV-RNA > 3 log(10) cp/ml and an available genotypic resistance test at baseline. At baseline, median CD4 counts and HIV-RNA were 278 cell/mmc and 4.32 log(10) cp/ml, respectively. Seventy-four subjects (30.2%) discontinued TDF and/or ddI, 23 of them for drug-related toxicities or intolerance. One-hundred and twenty-six (51.4%) subjects achieved virologic success (HIV-RNA < 50 copies/ml in two consecutive determinations) in a median time of 6.1 months; higher HIV-RNA levels (HR: 0.66, 95% CI: 0.54- 0.79, p < 0.001 for each additional log(10) copies/ml), and the total number of mutations either for PI and NNRTI at baseline (HR: 0.87, 95% CI: 0.81-0.92, p < 0.001 for each additional mutation) were both predictors of virologic success. M184V was marginally associated with virologic success (HR: 1.34, 95% CI: 0.94-1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not associated. One-hundred-thirty-three (54.3%) subjects achieved immunologic success (increase of > or = 100 cells/mm(3) from baseline) in a median time of 7.5 months; immunologic success was associated with HIV-RNA levels at baseline (HR: 0.91, 95% CI: 0.79-0.98, p = 0.04 for each additional log(10) copies/ml), the total number of mutations either for PI or NNRTI (HR: 0.91, 95% CI: 0.85-0.98, p = 0.01 for each additional mutation) and CD4 count at baseline (HR: 1.11, 95% CI: 1.00-1.23, p = 0.05 for each additional 100 cells/mm(3)). Results obtained by the on-treatment analyses were comparable. In our study, HAART containing TDF/ddI seem associated with a virologic and immunologic response, when such regimens are chosen according to a genotypic resistance test.

The V118I Mutation as a Marker of Advanced HIV Infection and Disease Progression

The V118I mutation is included in the nucleoside analogue mutations (NAMs) set. It contributes to thymidine-analogue resistance and, consequently, to resistance to the whole nucleoside reverse transcriptase inhibitor (NRTI) class. We focused on the V1181 mutation in order to evaluate factors associated with its detection and its relationship with HIV progression. Clinical and laboratory data at genotypic resistance test (GRT) of highly active antiretroviral therapy-failing patients were collected and their association with the V1181 mutation was analysed. Patients were also followed over time to determine factors related to progression to a new AIDS-related event or death. Of the 792 patients included, 114 (14.4%) carried the V118I mutation. In univariate analysis, the V118I mutation was significantly associated with a higher HIV RNA level, lower CD4+ T-cell count, Centers for Disease Control and Prevention (CDC) stage C, higher number of pre-GRT regimens and class-wide resistance (CWR) to NRTIs, protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Higher numbers of pre-GRT regimens and NRTI CWR were also associated in the multivariable analysis. Within the post-GRT observation period of up to 6 years (median: 72 months; interquartile range: 33-109) 107 events (58 new AIDS-related diseases and 49 deaths) were observed. Using the Cox proportional hazard model and the major clinical, behavioural and laboratory data, the V118I mutation was found to be associated with the endpoint (hazard ratio: 1.93, 95% confidence interval: 1.06-3.50; P=0.031). Other factors associated with disease progression were CDC stage C and lower CD4+ T-cell count at GRT. The analysis of our observational database suggests that the onset of the V118I mutation after treatment failure is unfavourable for the patient and can be considered a strong marker of disease progression.

The HIV RNA setpoint theory revisited.

BackgroundThe evolution of plasma viral load after HIV infection has been described as reaching a setpoint, only to start rising again shortly before AIDS diagnosis. In contrast, CD4 T-cell count is considered to show a stable decrease. However, characteristics of marker evolution over time depend on the scale that is used to visualize trends. In reconsidering the setpoint theory for HIV RNA, we analyzed the evolution of CD4 T-cell count and HIV-1 RNA level from HIV seroconversion to AIDS diagnosis. Follow-up data were used from two cohort studies among homosexual men (N = 400), restricting to the period before highly active antiretroviral therapy became widely available (1984 until 1996). Individual trajectories of both markers were fitted and averaged, both from seroconversion onwards and in the four years preceding AIDS diagnosis, using a bivariate random effects model. Both markers were evaluated on a scale that is directly related to AIDS risk.ResultsIndividuals with faster AIDS progression had higher HIV RNA level six months after seroconversion. For CD4 T-cell count, this ordering was less clearly present. However, HIV RNA level and CD4 T-cell count showed qualitatively similar evolution over time after seroconversion, also when stratified by rate of progression to AIDS. In the four years preceding AIDS diagnosis, a non-significant change in HIV RNA increase was seen, whereas a significant biphasic pattern was present for CD4 T-cell decline.ConclusionHIV RNA level has more setpoint behaviour than CD4 T-cell count as far as the level shortly after seroconversion is concerned. However, with respect to the, clinically more relevant, marker evolution over time after seroconversion, a setpoint theory holds as much for CD4 T-cell count as for HIV RNA level.

Predicting CD4-Cell Decline in HIV-Infected Patients

As a group, HIV-infected patients with high HIV RNA levels lose CD4 cells more rapidly than do those with low levels. However, rates of CD4-cell loss

Health literacy, antiretroviral adherence, and HIV-RNA suppression

Low health literacy has been associated with worse adherence to antiretroviral therapy (ART) and higher HIV-RNA levels, but these relationships have not been evaluated in longitudinal analyses. We evaluated literacy using the Rapid Estimate of Adult Literacy in Medicine (REALM) (< or = 6th grade, 7th to 8th grade, > or = 9th grade) in the HIV-Alcohol Longitudinal Cohort study of HIV-infected persons with a history of alcohol problems, conducted from 1997 to 2001. We tested HIV-RNA levels and administered a standardized questionnaire regarding demographics, substance use, receipt of ART, and adherence with ART, every 6 months for up to 7 occasions. Among the 235 subjects on ART, we investigated the relationship between literacy and 2 outcomes: 100% 3-day self-reported adherence and HIV-RNA suppression (<500 copies). Subjects' literacy levels were the following: 14% < or = 6th grade, 29% 7th to 8th grade, and 57% > or = 9th grade. In 66% of the observations (478/725), subjects reported 100% 3-day adherence with ART. Of the 685 HIV-RNA assays from these subjects, 62% had <500 copies. In unadjusted analyses, subjects with the lowest literacy level (< or = 6th grade) had a higher odds of adherence (odds ratio [OR] 2.23, 95% confidence interval 1.15 to 4.30) and HIV-RNA suppression (OR 2.01, 95% confidence interval 1.03 to 3.90) compared with those with > or = 9th grade literacy. This trend persisted but was no longer statistically significant in adjusted models of adherence (AOR 1.93, 95% confidence interval 0.86 to 4.31) and HIV-RNA suppression (AOR 1.70, 95% confidence interval 0.79 to 3.65). Contrary to our hypothesis, low literacy was not associated with a lower odds of adherence or virologic suppression in this longitudinal analysis of HIV-infected patients with a history of alcohol problems. Indeed, trends in these data suggest the possibility that low literacy may be associated with a higher odds of adherence and virologic suppression. These counterintuitive findings underscore the need to pursue a fuller understanding of the mechanisms by which literacy affects health outcomes.

Neutropenia in Human Immunodeficiency Virus Infection

Neutropenia is well described in individuals infected with human immunodeficiency virus (HIV) and occurs in approximately 10% to 50% of cases. Neither the effect of highly active antiretroviral therapy (HAART) on neutrophil counts nor the significance of neutropenia in terms of survival has previously been evaluated. The prevalence of neutropenia among 1729 HIV-infected women, followed up as part of the Women's Interagency HIV Study, was evaluated. The CD4 lymphocyte counts, HIV-1 RNA levels, and complete blood cell counts, including absolute neutrophil counts, were obtained at 6-month intervals. Neutropenia was common among HIV-infected women; at baseline, 44% had neutrophil counts less than 2000/microL, whereas 7% had counts less than 1000/microL. During 7.5 years of follow-up, neutrophil counts less than 2000/microL occurred on at least 1 occasion in 79%, whereas absolute neutrophil counts less than 1000/microL were documented in 31%. Worsening HIV disease parameters, such as lower CD4 cell counts (P<.001) and higher HIV-1 RNA levels (P<.001), were associated with development of neutropenia. Resolution of neutropenia was associated with higher CD4 cell counts (P<.001) and use of HAART (P=.007). We found that HAART, without zidovudine, was associated with protection against development of neutropenia. On multivariate analysis, neutropenia was not found to be associated with decreased survival among HIV-infected women. Worsening HIV disease parameters are associated with neutropenia in HIV-infected women. Treatment with HAART, without zidovudine in the regimen, protects against development of neutropenia, whereas HAART use and higher CD4 cell counts are associated with resolution of neutropenia. Neutropenia is not associated with decreased survival in HIV-infected women.

Incident High-Grade Squamous Intraepithelial Lesions in Senegalese Women With and Without Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2

Women infected with human immunodeficiency virus type 1 (HIV-1) and -2 may be at higher risk of developing cervical cancer than uninfected women. We assessed the relationships among human papillomavirus (HPV) types and persistence, HIV-1 and/or HIV-2 infection, and the development of high-grade cervical squamous intraepithelial lesions (HSILs) in a prospective study. We studied 627 women with and without HIV-1 and/or HIV-2 infection and high-risk HPV infection in Senegal, West Africa, who were assessed every 4 months for HSIL and HPV DNA over a mean follow-up of 2.2 years. Cox regression modeling was used to assess risks associated with development of HSIL. During follow-up, 71 (11%) of 627 women developed HSIL as detected by cytology. HIV-infected women with high-risk HPV types were at greatest risk for development of HSIL. In multivariable modeling, infection with oncogenic HPV types--both persistent (hazard ratio [HR] = 47.1, 95% confidence interval [CI] = 16.3 to 136) and transient (HR = 14.0, 95% CI = 3.7 to 54)--was strongly associated with HSIL risk. In univariate analyses, HIV-positive women infected with HIV-2 were less likely to develop HSIL (HR = 0.3, 95% CI = 0.1 to 0.9) than HIV-positive women infected with HIV-1. HIV-positive women with CD4+ cell counts between 200 and 500 cells per microliter (HR = 2.2, 95% CI = 0.8 to 6.3) or fewer than 200 cells per milliliter (HR = 5.5, 95% CI = 2.0 to 15.2) were at greater risk of HSIL than HIV-positive women with CD4 counts of more than 500 cells per milliliter. High plasma HIV RNA levels were associated with increased HSIL risk (HR for each order of magnitude increase in the level of plasma HIV RNA = 1.4, 95% CI = 1.1 to 1.7; P = .005). After adjustment for HPV types and persistence, however, HIV type, plasma HIV RNA level, and CD4 count were no longer statistically significantly associated with increased risk of HSIL. HIV-1 and HIV-2 are associated with increased risk for development of HSIL. This risk appears to be associated primarily with increased HPV persistence that may result from immunosuppression related to HIV-1 and/or HIV-2 infection.

Potential predictive factors of osteoporosis in HIV-positive subjects

Recent reports showed a high frequency of osteopenia/osteoporosis in HIV-infected subjects. Mechanism on the basis of this alteration is still unclear, as the direct effect of virus or of antiretroviral drugs. One hundred sixty-one consecutive HIV-infected outpatients aged 30–50 years, both naive and HAART-treated for >1 year, were included. An interview questionnaire was performed to establish prior pathological, toxic, epidemiological histories, medications intake, physical activity and eating habits. Blood and urinary tests were checked to exclude concomitant diseases, as were markers of bone metabolism and vitamin D3-metabolites. Each subject underwent to a lumbar spine and left hipbone mineral density by DEXA, using WHO criteria for diagnosis of osteopenia/osteoporosis. Radiologist was unaware if the subject was receiving HAART or not. For groups' homogeneity Chi-square, Fisher's exact and Student's t tests were used. Logistic regression analysis was used to find predictors of osteopenia/osteoporosis and linear regression model to find differences in bone mass density. The demographic characteristics of the 48 naive subjects and the 113 on HAART were comparable. Eighty subjects (49.7%) showed osteopenia/osteoporosis: 22 (45.8%) naive and 58 (51.3%) on HAART ( P = 0.46). Independent predictors of osteopenia/osteoporosis were female gender (OR: 3.02, 95% CI: 1.26–7.25, P = 0.01 vs. male), older age (OR: 1.10, 95% CI: 1.01–1.20, P = 0.03, for each additional year), low body mass index (OR: 0.78, 95% CI: 0.68–0.91, P = 0.001 for each additional unit) and higher HIV-RNA levels at DEXA (OR: 1.97, 95% CI: 1.16–3.34, P = 0.01 for each additional Log 10), whereas the use of HAART (OR: 2.61, 95% CI: 0.66–10.27, P = 0.17 vs. naive) and the alterations of markers of bone metabolism were not significantly related to osteopenia/osteoporosis. Similar findings were obtained using linear regression model analysis. HIV-infected subjects have a high frequency of osteopenia/osteoporosis. Traditional risk factors are predictive of osteopenia/osteoporosis also in HIV-subjects; the association with higher HIV-RNA levels can suggest a direct role of HIV itself in the occurrence of bone disease.

Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients

To evaluate the effect of drug class-wide resistance (CWR) on survival in HIV-infected individuals who underwent genotypic resistance test after antiretroviral failure. Observational, longitudinal cohort study. HIV-infected individuals experiencing treatment failure were enrolled at first genotypic resistance test. End-points were death for any cause, AIDS-related death and AIDS-defining event/death. CWR was defined according to the International AIDS Society consensus. Survival analysis was performed with Cox's model. Among 623 patients enrolled and followed for a median of 19 months (interquartile range, 12-29), Kaplan-Meier analyses for end-points at 48 months in patients with no CWR, one CWR, two CWR or three CWR were 8.9, 11.7, 13.4 and 27.1%, respectively, for death; 6.1, 9.9, 13.4 and 21.5%, respectively, for AIDS-related death; and 16.0, 17.7, 19.3 and 35.9%, respectively, for new AIDS event/death. In a multivariate Cox's model, higher HIV RNA level, previous AIDS and detection of three CWR (hazard ratio, 5.34; 95% confidence interval, 1.76-16.24) were all significantly associated with increased risk of death, while higher CD4 cell count and use of a new boosted protease inhibitor drug after identifying genotypic resistance were associated with reduced risk. Detection of three CWR was also significantly associated with higher risk of AIDS-related death and new AIDS event/death. Even in the late era of highly effective antiretroviral treatments, detection of CWR, particularly if extended to all three drug classes is related to poorer clinical outcome and represents a risk-marker of disease progression and death.

Lipodystrophy Is Associated With a Low Rate of Treatment Failure in HIV-Positive Patients Switched to Atazanavir

Lipodystrophy Is Associated With a Low Rate of Treatment Failure in HIV-Positive Patients Switched to Atazanavir

Factors and Temporal Trends Associated With Highly Active Antiretroviral Therapy Discontinuation in the Women's Interagency HIV Study

We characterized factors and temporal trends associated with discontinuation of highly active antiretroviral therapy (HAART) among 936 HIV-infected women enrolled in the Women's Interagency HIV Study. A multivariate analysis of post-HAART initiation exposures found that high HIV RNA levels (relative hazard [RH] = 1.36, P < 0.001) and high depressive symptom scores (RH = 1.53, P = 0.012) were associated with HAART discontinuation. The adjusted hazard of discontinuation was higher in the 2 most recent calendar periods compared with the first (RH = 1.61, P = 0.026; RH = 1.56, P = 0.074, respectively). The increasing risk of HAART discontinuation in recent calendar periods and changes in the clinical factors associated with discontinuation reflect ongoing and dynamic shifts in the approach to HAART utilization.

Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral‐naïve cohort

With the use of potent antiretroviral therapy in patients with HIV disease, changes in lipid parameters and glucose homeostasis have been noted. However, these effects have been difficult to interpret because of the varied demographic and treatment characteristics of the cohorts and the complexity of differentiating the effect of HIV disease from that of the drugs used in its treatment. This study was designed to explore these issues. Demographic information and fasting blood samples were collected from 419 antiretroviral-naive HIV-1-infected patients. The average age of the participants was 38.2 years, with 21% being female, 60% being African American, and 14% having a history of injection drug use. The mean CD4 lymphocyte count was 216 cells/microL, the mean baseline log10 HIV viral load was 4.98 HIV-1 RNA copies/mL, and 26% of patients had a history of AIDS-defining events. Women and African Americans had significantly higher levels of high-density lipoprotein (HDL) cholesterol, and older age was associated with higher total cholesterol levels. Lower CD4 lymphocyte counts and higher HIV RNA levels were independently associated with lower HDL cholesterol levels. Additionally, higher HIV RNA level was associated with lower levels of low-density lipoprotein (LDL) cholesterol and higher levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides. A history of AIDS-defining events was associated with higher total cholesterol, VLDL cholesterol and triglyceride concentrations. With respect to glucose homeostasis, a higher CD4 lymphocyte count was associated with less evidence of insulin resistance. However, a higher body mass index was associated with higher lipid levels and with more evidence of insulin resistance. Both HIV disease and demographic characteristics were found to influence lipid values and glucose homeostasis in the absence of antiretroviral treatment. More advanced HIV disease was associated with less favourable lipid and glucose homeostatic profiles. The independent association between HIV RNA levels and various lipid parameters suggests that viral replication had a direct effect on lipid levels. Interpretation of the effects of various HIV treatment regimen and drugs on metabolic parameters must take into account the stage of HIV disease and the demographic characteristics of the population studied.

Low CD4+ cell counts and high HIV-1 RNA levels after HAART predict poor prognosis in HIV-positive women

Low CD4+ cell counts and high HIV-1 RNA levels after HAART predict poor prognosis in HIV-positive women

Persistent HIV-1 replication does not explain low levels of T-cell interferon-gamma mRNA and elevated serum NO(2) (-)/NO(3) (-) in patients with stable CD4 T-cell responses to HAART.

HIV-1 infected patients adherent to HAART and displaying stable increases in CD4 T-cell counts differ in their control of HIV replication and one might expect this to reflect depressed immune function. The importance of virological control in functional immune reconstitution was investigated in HIV-1 infected patients who maintained high or undetectable plasma HIV RNA levels over 2-4 years on HAART (discordant and complete responders, respectively). Immunocompetence and immune activation were assessed directly ex vivo and after a short period of culture, as HIV replication in cultures from viraemic patients may artificially depress responses. Expression of cytokine (interferon-gamma, interleukin-5) and chemokine receptor (CCR5, CRTH2) mRNA were determined and soluble CD30 and NO(2) (-)/NO(3) (-) were measured in sera. Unstimulated cells from all patients had low levels of IFNgamma mRNA relative to uninfected controls. Discordant responders had more IFNgamma, IL-5 and CCR5 mRNA in mitogen-stimulated PBMC than complete responders, where the difference could be attributed to CD8-T-cells. Serum NO(2) (-)/NO(3) (-) levels were significantly higher in all patients than controls, with no difference between complete and discordant responders. Serum CD30 levels were significantly higher in discordant responders. These data indicate a persistent immune deficit in immune reconstituted patients irrespective of HIV viral load and associate persistent viral replication with lymphocyte activation, probably involving CD8 T-cells.

Early markers of HIV-1 disease progression in a prospective cohort of seroconverters in Bangkok, Thailand: implications for vaccine trials.

Some candidate HIV-1 vaccines may not prevent HIV-1 infection but may alter the course of disease. Surrogate endpoints based on early laboratory makers in HIV-1-infected persons who are antiretroviral therapy (ART)-naive will be useful for evaluating vaccine efficacy in slowing disease progression (VEp). We examined pretreatment HIV-1 viral loads and CD4 cell counts in recent HIV-1 seroconverters to inform selection of these endpoints. We studied 130 newly HIV-1-infected injection drug users identified from a prospective cohort of initially uninfected persons in Bangkok during 1995 through 1998. We analyzed trends in HIV-1 viral loads and CD4 cell counts as well as progression to the surrogate endpoint, defined as 2 consecutive CD4 cell counts of fewer than 350 cells/mm, during 24 months after the first HIV-1 seropositive (FP) visit. Median HIV-1 RNA copies/mL with interquartile ranges were 43,693 (14,320-94,767) at the FP visit, 46,924 (16,273-104,314) at 6 months, 28,446 (11,292-54,325) at 12 months, and 18,080 (8713-54,059) at 18 months. HIV-1 viral loads at the FP visit and at 18 months were positively correlated (r = 0.53, P < 0.0001). Of 130 participants, 12% reached the surrogate endpoint by 6 months, 16% by 12 months, and 27% by 18 months. In Cox regression analyses, HIV-1 viral loads of more than 50,000 copies/mL at the FP visit (hazard ratio [HR] = 2.3, 95% confidence interval [CI]: 1.1-4.8) and first CD4 cell count of 500 or fewer cells/mm (HR = 7.6, 95% CI: 3.2-17.6) were independently associated with faster progression to the surrogate endpoint. Participants with high HIV-1 RNA levels and low CD4 cell counts close to the time of seroconversion were more likely to experience early immunologic progression. Approximately one quarter of seroconverters reached the surrogate immunologic endpoint within 18 months of their FP visit and before starting ART, suggesting the utility of this endpoint for analyses of VEp in some ongoing and planned HIV-1 vaccine efficacy trials.

Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy.

Among 470 patients with acquired immune deficiency syndrome and/or human immunodeficiency virus infection (HIV/AIDS) who underwent genotype resistance testing (GRT) after the failure of therapy, 17 (3.6%) harbored the Q151M mutation. The Q151M mutation was associated with younger age, lower CD4(+) lymphocyte count, higher HIV RNA level, and treatment with >2 pre-GRT regimens. By contrast, the Q151M mutation was inversely associated with lamivudine administration. A full reversion of the Q151M mutation was observed in 5 of 5 patients who underwent treatment interruption after GRT. The reversion was followed by a response to salvage therapy in 4 (80%) of 5 patients.

Predictors of sustained response to therapy resumption after treatment interruption in HIV-infected patients failing antiretroviral therapy.

In order to evaluate whether a sustained virologic response to therapy resumption after treatment interruption can be achieved in the setting of virologic failure, we reviewed retrospectively the data relating to 56 human immunodeficiency virus (HIV)-infected subjects selected from 3,145 patient charts. At the time of treatment interruption (study entry), the median (interquartile range) CD4+ counts and HIV-RNA levels were respectively 247 (127-502) x 10(6) cells/L and 4.24 (3.68-5.02) log(10) copies/ml, and the patients had been exposed to eight (5-9) antiretroviral drugs. After treatment interruption, the patients received at least three drugs depending on their treatment history. Forty-eight weeks after the resumption of therapy, 19 of the 56 patients (34%) had HIV-RNA levels of <400 copies/ml and, in comparison with study entry, the difference in the median increase in CD4+ counts between the virologic responders and non-responders (83 vs. 8.5 x 10(6) cells/L) was statistically significant (P = 0.02). Multivariate analysis showed that higher peak HIV-RNA levels before treatment interruption were independently predictive of virologic failure, whereas a longer treatment interruption period independently correlated with a virologic response. Four patients with CD4+ counts of <200 x 10(6) cells/L at study entry developed HIV-related clinical events. A sustained virologic response to therapy resumption after treatment interruption can be achieved in the setting of virologic failure. An evaluation of clinical history may help to identify the patients who are more likely to respond.