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Sundhiya Mandalia

Publications and source records attributed to Sundhiya Mandalia.

At least 19 recordsLinked to original sources
PubMed2006

An open-label, randomized comparative pilot study of a single-class quadruple therapy regimen versus a 2-class triple therapy regimen for individuals initiating antiretroviral therapy.

OBJECTIVE: To examine the antiviral potency and tolerability profile of a single-class four drug (quadruple) nucleoside reverse transcriptase inhibitor (NRTI) regimen compared with a 2-class standard-of-care regimen. METHODOLOGY: A three-centre, randomized, open-label comparative pilot study of zidovudine/lamivudine/efavirenz (triple) versus abacavir/lamivudine/zidovudine/tenofovir (quadruple) therapy in HIV-1-infected, treatment-naive individuals. Both regimens were taken without regard to food and consisted of a twice-daily regimen and 3 pills/day. The study power was based on time-weighted average changes in HIV-1 RNA load. RESULTS: A total of 114 individuals (56 triple, 57 quadruple) received at least one dose of medication. Patients were well matched at baseline for viral load (mean 5.26 log10 versus 5.13 log10, respectively) and CD4 cell count (median 193 versus 153 cells/mm3, respectively). The two regimens performed similarly with regards to all endpoints. At week 48, by intention-to-treat, missing=failure analysis, 68% of triple- and 67% of quadruple-drug treated patients had an HIV-1 RNA <50copies/ml (P>0.05). On-treatment analysis showed 40/40 (100%) of triple- and 39/40 (97.5%) of quadruple-drug treated patients (P=0.996) had responded to <50copies/ml. No unexpected adverse events were reported. Changes in total cholesterol and triglycerides were modest but significantly favoured the quadruple therapy regimen at multiple time points. CONCLUSION: This pilot study suggests a quadruple NRTI-based regimen provides similar antiviral potency, tolerability and administrative characteristics to a 2-class triple therapy regimen. These findings should be confirmed in a more fully powered study. Potent quadruple NRTI-based regimens may have advantages for some individuals with regards to salvageability, tolerability and drug interactions.

Adenine↗
PubMed2005

Cost-effectiveness of highly active antiretroviral therapy in South Africa.

BACKGROUND: Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. METHODS AND FINDINGS: Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19) for the HAART group versus 3.73 (95% CI: 3.55-3.97) for the No-ART group, and 8.71 (95% CI: 8.40-9.03) versus 4.35 (95% CI: 4.12-5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52) for the HAART versus 15.36 (95% CI: 13.97-16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49) compared with 6.60 (95% CI: 5.69-7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per LYG was cost saving for both scenarios. In a sensitivity analysis based on the lower (25%) and upper (75%) interquartile range survival percentiles, the incremental cost per LYG ranged from $1,557 to $1,772 for the group without AIDS and from cost saving to $111 for patients with AIDS. CONCLUSION: HAART is a cost-effective intervention in South Africa, and cost saving when HAART prices are further reduced. Our estimates, however, were based on direct costs, and as such the actual cost saving might have been underestimated if indirect costs were also included.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Transmission of hepatitis C virus among HIV-positive homosexual men and response to a 24-week course of pegylated interferon and ribavirin.

OBJECTIVE: To evaluate treatment outcome of acute hepatitis C virus (HCV) in HIV-positive individuals. DESIGN: Open-label, prospective study conducted in London, January 1997-December 2003. METHODS: Patients in whom acute HCV infection had been diagnosed had sequential HCV RNA levels measured at 0, 4, 12, 24, 32, and 48 weeks. If HCV RNA positive at 12 weeks, patients were offered pegylated interferon alpha-2b 1.5 microg/kg/wk and ribavirin 800-1200 mg/d for 24 weeks. Patients with increasing HCV RNA titers were offered treatment earlier. RESULTS: Fifty male homosexuals with a mean age 37 years were identified: 44 from abnormal liver function test results, 4 from sexual contact with an HCV-positive partner, and 2 at HIV seroconversion. Overall, 12 individuals became HCV RNA negative spontaneously. This was significantly associated with high baseline median CD4(+) count (P = 0.029), CD4(+) count >500 cells/mm(3) (P = 0.017), and lower HCV RNA titers (P = 0.017). Only 27 patients accepted treatment, 16 (59%) of whom reached sustained virologic response. This was associated with higher peak mean alanine aminotransferase (P < 0.001) and higher baseline CD4% (P = 0.041). CONCLUSIONS: Sustained virologic response rates in HIV-positive patients treated for acute HCV infection are lower than in HIV-negative subjects. Because a high percentage of individuals seroconvert spontaneously, treatment should be delayed until after 12 weeks.

Acute Disease↗
PubMed2005

A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy.

BACKGROUND: The established International Prognostic Index for lymphomas has not included patients with systemic AIDS-related non-Hodgkin lymphoma. OBJECTIVE: To establish the most appropriate prognostic index for use in patients with systemic AIDS-related non-Hodgkin lymphoma. DESIGN: A prospective study involving univariate and multivariable analyses of patients with AIDS-related non-Hodgkin lymphoma whose data were used to examine standard and new criteria for survival after diagnosis. SETTING: The Chelsea and Westminster cohort of HIV-1-infected persons. PATIENTS: 9621 HIV-positive patients, 111 in whom AIDS-related non-Hodgkin lymphoma was treated after 1996, in the era of highly active antiretroviral therapy (HAART). INTERVENTION: Cox proportional hazards regression analysis to determine the prognostic significance of multiple clinicopathologic variables. RESULTS: Survival of patients with AIDS-related non-Hodgkin lymphoma has increased in the HAART era (log-rank chi-square, 9.23; P = 0.002). Univariate analyses using the established International Prognostic Index factors of age, tumor stage, lactate dehydrogenase level, Eastern Cooperative Oncology Group performance status, and number of extranodal sites were confirmed to be significant variables. Regression modeling for patients in whom disease was diagnosed after 1996 revealed only 2 independent predictors of death: International Prognostic Index risk group and CD4 cell count. These predictors yielded 4 internally validated risk strata with predicted 1-year survival rates of 82%, 47%, 20%, and 15% (P < 0.001). Prognostic risk scores in the highest quartile yielded a likelihood ratio for death of 7.90 (hazard ratio, 1.0), whereas a prognostic score less than 1.0 yielded a likelihood ratio of 0.23 (hazard ratio, 0.15 [95% CI, 0.06 to 0.33]). LIMITATIONS: The sample was small, and different HAART regimens were used. CONCLUSIONS: For patients with AIDS-related non-Hodgkin lymphoma that was diagnosed in the era of HAART, application of the International Prognostic Index remains useful. The addition of CD4 cell count provides further independent prognostic information. Patients who present with AIDS-related non-Hodgkin lymphoma and a low CD4 cell count have a poor prognosis; this information can be used to guide therapeutic options.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Hepatitis C infection is not associated with systemic HIV-associated non-Hodgkin's lymphoma: a cohort study.

Immunosuppression induced by the human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin's lymphoma (NHL). As the hepatitis C virus (HCV) has been implicated in the development of B cell lymphomas, we compared the incidence of systemic NHL during HIV infection compared to HIV and HCV co-infection. Of 5,832 individuals studied during the era of highly active anti-retroviral therapy (HAART), 102 patients were diagnosed with systemic NHL. The incidence of systemic NHL was 6.9 of 10(4) patient years during HIV infection compared to 7.1 of 10(4) patient years during HIV alone (p = 0.9). In this immunocompromised patient population, there was no association between HCV infection and an increased risk of lymphoma.

Cohort Studies↗
PubMed2005

Hepatitis C virus infection in HIV type 1-infected individuals does not accelerate a decrease in the CD4+ cell count but does increase the likelihood of AIDS-defining events.

Human immunodeficiency virus type 1 (HIV-1) appears to adversely affect hepatitis C, but whether hepatitis C virus (HCV) has a reciprocal effect on HIV-1 infection remains a point of controversy. In a multivariate analysis of a cohort of 5832 individuals, we found that individuals coinfected with HCV and HIV-1 (prevalence of coinfection, 5.8%) had a CD4+ cell count that decreased at a rate similar to that for individuals infected with HIV-1 alone. However, coinfection was associated with a statistically significant increased likelihood of onset of an acquired immunodeficiency syndromedefining illness or developing a CD4+ cell count of <200 cells/mm3, compared with infection with HIV-1 alone (hazard ratio, 1.52; 95% confidence interval, 1.072.17). Patients who were naive to highly active antiretroviral therapy were significantly less likely to progress to either end point, because of their higher CD4+ cell counts. In conclusion, there was an increased number of adverse events in coinfected individuals, compared with individuals infected with HIV-1 alone.

Adult↗
PubMed2005

Early virologic failure in HIV-1 infected subjects on didanosine/tenofovir/efavirenz: 12-week results from a randomized trial.

OBJECTIVE: To compare the safety and efficacy of two once-daily antiretroviral regimens containing lamivudine (3TC) or tenofovir disoproxil fumarate (TDF), each administered with didanosine (ddI) and efavirenz (EFV) as initial therapy to HIV-1-infected subjects. METHODS: Single centre, randomized (1: 1), open-label study in antiretroviral-naive, HIV-infected adults. Subjects commenced either 3TC/ddI/EFV (3TC group) or TDF/ddI/EFV (TDF group). Safety, Medication Event Monitoring System (MEMScap) and plasma EFV concentration monitoring was performed over the study period. Comparisons between groups were assessed using chi test and linear regression analysis was used to assess the relationship between EFV concentrations and virological response. RESULTS: Seventy-seven subjects were enrolled prior to recruitment being suspended, 36 to the 3TC group and 41 to the TDF group. Intention-to-treat analysis in which last observation carried forward (LOCF) found the mean viral log10 load [95% confidence interval (CI)] at weeks 4 and 12 to be 2.67 (2.47-2.87) and 1.83 (1.74-1.92) for the 3TC group and 2.75 (2.45-3.05) and 2.28 (1.96-2.6) for the TDF group (P = 0.013). Emergence of resistance occurred in five of 41 (12.2%) subjects in the TDF group up to week 12 compared with none of 36 in the 3TC group, (P < 0.05); these five subjects shared similar baseline characteristics (CD4+ cell counts < 200 x 10 cells/l and HIV-1 RNA > 100,000 copies/ml). Despite MEMScap monitoring showing > 99% adherence in all subjects, among the five failures, three had low EFV concentrations. CONCLUSION: TDF/ddI/EFV as initial therapy appears to have diminished efficacy in subjects with CD4 < 200 x 10 cells/l and viral load > 100,000 copies/ml. Treatment failure with resistance was not attributable to baseline resistance, efavirenz exposure or poor adherence.

Adenine↗
PubMed2005

Adherence to trizivir and tenofovir as a simplified salvage regimen is associated with suppression of viraemia and a decreased cholesterol.

BACKGROUND: Treatment failure during highly active antiretroviral therapy (HAART) is ultimately common and associated with the development of resistance mutations. Trizivir (zidovudine/lamivudine/abacavir) and tenofovir disoproxil fumarate may improve adherence and enhance virological suppression in individuals who have failed previous regimens. METHODS: Individuals were identified who had failed previous HAART and who were then prescribed trizivir and tenofovir. Viral load and genotypic information were obtained to assess virological response. RESULTS: One hundred and twenty-two individuals were identified from a database containing 5883 patients. In a last observation carried forward intention to treat analysis, 34% of individuals achieved an undetectable viral load of <50 copies/mL at 1 year. Of those who were able to remain on treatment for 1 year, 65% achieved undetectability. We observed no effect regarding previous regimens on viral outcome. Accumulation of TAMs (thymidine analogue mutations) was associated with a decrease in the number of patients achieving an undetectable viral load (with <2 TAMs present 38% of patients developed undetectable viral loads, > or =1;2 TAMs 17% undetectable; P = 0.03). Using the mean cell volume as a measure of compliance, those with higher values were more likely to achieve a viral load <50 copies/mL (P = 0.04). A beneficial effect on cholesterol was noted regardless of virological outcome. CONCLUSIONS: In compliant heavily pre-treated individuals with less than 2 TAMs, salvage therapy with trizivir and tenofovir is associated with suppression of viraemia and an improved lipid profile.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection.

BACKGROUND: CXCR4-using virus is associated with higher viral load and accelerated human immunodeficiency virus (HIV) disease progression. Additionally, CCR5 antagonists may not reduce the HIV-1 RNA load when mixed/dual-tropic or CXCR4-using virus is present. The determination of coreceptor tropism may be required before CCR5 or CXCR4 antagonists are initiated, unless reliable predictive markers of coreceptor use are established. METHODS: Samples from treatment-naive and -experienced HIV-1-positive individuals with date-matched CD4 and CD8 cell counts and HIV-1 RNA, clade, and pol sequences were assessed for coreceptor usage, by use of the ViroLogic PhenoSense assay. RESULTS: Coreceptor use determination was successful in 563 of 861 samples. Non-clade B virus was present in 18.6% of samples. CXCR4 or mixed/dual-tropic CCR5/CXCR4 virus was present in 112 of samples (19.9%). Only 4 samples (0.7%) showed exclusive CXCR4 use. In a multivariate model, higher CD4 cell count, lower viral load, and higher natural killer cell counts were significantly associated with CCR5 usage. No associations with treatment experience, clade, or pol gene mutations were observed. CONCLUSION: The prevalence of CCR5-tropic HIV-1 phenotype declines with decreasing CD4 cell count and increasing viral load. Mixed/dual tropic virus is found in all CD4 cell count and viral load strata. Coreceptor usage is not influenced by viral clade.

Adult↗
PubMed2005

Clinical characteristics of IRIS syndrome in patients with HIV and tuberculosis.

BACKGROUND: Some patients with HIV/tuberculosis (TB) coinfection who are on anti-TB treatment and highly active antiretroviral therapy (HAART) will develop an exacerbation of symptoms, signs or radiological manifestations of TB that are not due to relapse or recurrence of their TB. The aetiology of these immune reconstitution inflammatory syndrome (IRIS) reactions is unknown but it is presumed that they occur, at least in part, as a consequence of HAART-related reconstitution of immunity. METHODS: Patients who were diagnosed with their first episode of definitive or presumed TB between January 2001 and July 2003 were identified from the Chelsea and Westminster TB/HIV database. The patients were classified into those who developed IRIS and those who did not using a set definition of the syndrome. Demographic, clinical and laboratory data relating to both HIV and TB were compared between the two groups. RESULTS: A total of 55 cases of TB were identified, of which 45 cases were confirmed on culture or gene probe and 10 were presumed cases. Fourteen cases (25.5%) developed IRIS with a median (range) duration of 2.53 (0.53-14.97) months. The median baseline CD4 [interquartile range (IQR)] for the IRIS group was significantly lower at 80 (33-117) cells/mm3 (P = 0.05) than the non-IRIS group at 139 (77-284) cells/mm3. A significantly greater proportion of patients in the IRIS group [11/14 (78.60%), P = 0.011] had baseline CD4 < 100cells/mm3 compared with the non-IRIS group [16/41 (39.0%)]. There was no significant difference between the two groups when comparing the log10 baseline viral load (VL). Eight (57.0%) patients in the IRIS group had disseminated TB at baseline compared with seven (17.0%) in the non-IRIS group (P = 0.006). In those who had a detectable VL at baseline, the median fold change (IQR) in CD4 from baseline to 3 months was significantly higher in the IRIS group patients, 1.5 (0.6-5.6), compared with 0.7 (-0.2 to 1.0) for those in the non-IRIS group (P = 0.046). CONCLUSIONS: Patients who develop IRIS are more likely to present with disseminated TB, have a CD4 count < 100 cells/mm3 and have a prompt rise in CD4 count in the initial 3 months of HAART.

Adult↗
PubMed2004

A randomized study comparing a three- and four-drug HAART regimen in first-line therapy (QUAD study).

BACKGROUND: Evidence from randomized controlled trials supports the use of triple therapy. Research is required on the effectiveness of quadruple therapy in comparison to this and the relative effectiveness of specific highly active antiretroviral therapy (HAART) combinations. METHODS: Antiretroviral-naive individuals (n = 53) with an HIV-1 viral load >100 000 copies/mL were randomized to receive three-drug HAART with zidovudine/lamivudine (Combivir) and efavirenz or quadruple therapy with zidovudine/lamivudine/abacavir (Trizivir) and efavirenz (quad regimen). Patients continued on HAART for 48 weeks with regular clinical and immunological assessment. Standard and ultrasensitive (<5 copies/mL) viral load testing was carried out. RESULTS: A DAVG (difference in averages) analysis of the fall in viral load and increase in CD4 count showed no significant differences between regimens. Triple therapy resulted in a -4.17 log change (95% CI, -4.48 to -3.85) and quadruple therapy in a -4.36 log change (95% CI, -4.68 to -4.03) in viral load. For CD4 counts, the triple therapy arm increased by 164 cells/mm(3) (95% CI 112-217) and the quadruple arm by 185 (95% CI, 133-237). In an intent-to-treat analysis, 77% of patients in the triple therapy group reached an undetectable viral load (<50 copies/mL) compared with 84.2% of the quadruple therapy group. For ultrasensitive viral load testing, 23% and 18% of each group, respectively, reached undetectable viral loads. The hazard ratio for attaining a viral load of <5 copies/mL was 0.59 (95% CI, 0.26-1.33) for quadruple versus triple therapy. Three individuals in the triple therapy arm and nine in the quadruple therapy arm discontinued treatment. CONCLUSIONS: No differences in any analyses were observed between a standard of care regimen (zidovudine/lamivudine and efavirenz) and the quad regimen (zidovudine/lamivudine/abacavir and efavirenz).

Alkynes↗
PubMed2004

The cost-effectiveness of highly active antiretroviral therapy, Canada 1991-2001.

AIM: To estimate the cost-effectiveness ratio of highly-active antiretroviral therapy (HAART) in Canada. DESIGN: A before-and-after analysis to calculate incremental cost of life year gained (LYG) between 1991 and 1995 (pre-HAART period) and between 1997 and 2001 (HAART period) for non-AIDS and AIDS groups (CDC stage of HIV infection). METHODS: For two Quebec HIV hospital clinics, mean inpatient (IP) days, outpatient (OP) visits and direct health care costs per patient-year (PPY) were calculated. Cox's proportional hazards models calculated disease progression, stratified by study periods and adjusted for gender, age at cohort entry, sexual orientation, injecting drug use and baseline CD4 cell count. RESULTS: For non-AIDS patients, mean IP days was 1.6 (pre-HAART period) compared with 0.8 PPY (HAART period); mean OP visits increased from 2.8 to 5.5 PPY. Total cost was US$ 4265 (pre-HAART period) and US$ 9445 PPY (HAART period) of which 66 and 84%, respectively were spent on antiretroviral drugs. Median progression time was 6.3 years in the pre-HAART period compared with 12.5 years in HAART period (log rank chi = 270, P < 0.0001). Incremental cost per LYG between periods was US$ 14 587. For AIDS patients, mean IP days decreased from 13.3 to 4.4 PPY between periods; OP visits increased from 8.3 to 9.2 PPY. Total costs increased from US$ 9099 to US$ 11 754 PPY, while expenditure on antiretroviral drugs increased from 29 to 72% of total cost. Median progression time was 3.8 years in the pre-HAART period, which increased to 13.3 years in the HAART period (log rank chi = 158, P < 0.0001); incremental cost per LYG between periods was US$ 12 813. CONCLUSION: HAART appeared a cost-effective intervention in Canada.

Acquired Immunodeficiency Syndrome↗