Virological outcome and frequency of low-level viremia in patients receiving generic dolutegravir-containing regimen at a large tertiary care clinic in Western India.

BACKGROUND: Dolutegravir (DTG) is widely used for the management of naïve and treatment-experienced HIV-infected patients. Low-level viremia (LLV) is common in patients receiving nonnucleoside reverse transcriptase inhibitor- and protease inhibitor-containing regimens. However, the incidence of LLV associated with DTG-containing regimen is not well known. OBJECTIVE: The objective of this study was to assess the virological response associated with DTG-containing regimens and explored frequencies of LLV and risk factors for the same. METHODS: We performed a retrospective cohort study of HIV-infected patients receiving generic DTG-containing regimen from February 2017 to July 2019. All adult patients (≥18 years), who completed at least the first follow-up after initiating treatment, were included in this study. LLV was defined as plasma viral load between 20 and 200 copies/ml. RESULTS: A total of 597 patients started DTG-containing regimen during the study period, of which 522 patients met the inclusion criteria. The study patients were categorized into five groups: naïve (n = 86), first-line failure (n = 32), second-line failure (n = 53), switch (n = 325), and HIV-2 (n = 26). Complete virological suppression at 6, 12, and 18 months was achieved in 78.5%, 81.1%, and 70.9% of the patients, respectively. Furthermore, 17.9%, 12.9%, and 23.3% of the patients had LLV at 6, 12, and 18 months, respectively. Persistent LLV was found in 2.9% of the patients. Overall, DTG was well tolerated and was discontinued in only three patients due to neuropsychiatric side effects. CONCLUSION: DTG is well tolerated and effective in suppressing HIV across all antiretroviral treatment categories. The rate of persistent LLV is low in DTG-containing therapy.

Comparison of the Effectiveness of Low-Dose Indinavir/Ritonavir (IDV/r)- versus Atazanavir/Ritonavir (ATV/r)-Based Generic Antiretroviral Therapy in NNRTI-Experienced HIV-1-Infected Patients in India.

BACKGROUND: Currently, data on the effectiveness of second-line antiretroviral regimens using indinavir/ritonavir (IDV/r) and atazanavir/ritonavir (ATV/r) along with 2 nucleoside reverse transcriptase inhibitor (NRTI) in resource-poor settings is limited. METHODS: Observational follow-up study on 441 patients who experienced treatment failure to first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment. Multivariate Cox Proportional Hazards Model was used to assess comparative effectiveness of treatment regimens. RESULTS: A total of 63 patients (14.8%) had failed second line treatments, of which 53 patients (17.2%) were using IDV/r while 10 patients (8.5%) were on ATV/r. After adjusting for age, weight, gender, and baseline CD4 count, patients who took IDV/r were more than twice as likely to experience treatment failure as compared to those who were on ATV/r (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.14, 4.15). Successful response to second-line therapy was not different between the 2 treatment groups when patients weighed less than 55 kg at baseline (log rank P value = 1.00) in contrast to the individuals weighing ≥55 kg (P < .0001). CONCLUSION: We found that successful response to second-line therapy was twice as likely in the ATV/r group; however, this difference was eliminated in patients less than 55 kg.

Management of cryptococcal meningitis in HIV-infected patients: Experience from western India.

INTRODUCTION: Cryptococcal meningitis is one of the acquired immunodeficiency syndrome defining infections with high mortality. Amphotericin B is the preferred drug for induction therapy. Despite advances in human immunodeficiency virus (HIV) treatment, Antiretroviral Treatment (ART) roll-out programs and availability of amphotericin B, cryptococcal meningitis remains an important cause of mortality in the African and other developing countries. MATERIALS AND METHODS: We carried out a prospective observational study to determine the treatment response rate, tolerability and outcome of patients with cryptococcal meningitis in HIV treated with amphotericin B. Descriptive statistic was used to analyze the data. RESULTS: A total of 27 patients were diagnosed with cryptococcal meningitis during the study period. Headache (96.29%) was the single most common presenting symptom of cryptococcal meningitis in HIV-infected patients, followed by vomiting (77.77%) and fever (66.66%). Cerebrospinal fluid (CSF) routine and microscopic examination was within normal limits in six patients. CSF became sterile on the 12th day of Amphotericin B in 55.55% of the patients while 33.33% had positive CSF cultures. Patients were started with ART after achieving sterile CSF and tolerated at least 2 weeks of fluconazole consolidation treatment and were free from symptoms. Median time for antiretroviral treatment initiation was 35 (14-90) days after completion of Amphotericin B treatment. One patient developed immune reconstitution inflammatory syndrome (IRIS) after ART. CONCLUSIONS: We found that the recommended 2 weeks induction treatment with Amphotericin B monotherapy for HIV patients with cryptococcal meningitis in resource-limited settings may be suboptimal for at least one-third of the patients. Extending the therapy to 3 weeks is likely to result in sterilization of the CSF in a majority of these patients. This finding requires confirmation by a larger sample size in appropriately powered studies. Delaying ART initiation by at least 2 weeks after amphotericin B treatment may decrease the incidence of IRIS.

Tenofovir-associated renal dysfunction in clinical practice: An observational cohort from western India.

BACKGROUND: Tenofovir (TDF) is preferred nucleoside reverse transcriptase inhibitors (NRTI) for the treatment of human immunodeficiency virus infection because of its potency and safety. Renal toxicity with TDF use is low and comparable with other NRTI in clinical trials, but there are many case studies and small case series of renal dysfunction with TDF. MATERIALS AND METHODS: This is an observational longitudinal cohort of patients started on a TDF-based regimen from January 2007 to April 2010. Patients were evaluated at baseline and with every follow-up visit for serum creatinine and calculated creatinine clearance (Cockroft-Gault formula). In addition to this, the patients were also subjected to test for serum potassium, phosphorous and urine examinations as and when indicated. Renal dysfunction was defined as rise in serum creatinine to more than the upper level of normal (>1.2 mg%). RESULTS: Of 1,271 patients started on a TDF-containing antiretroviral treatment (ART) 83 (6.53%) developed renal dysfunction, of which 79 had impaired serum creatinine and five had Fanconi's syndrome. Renal dysfunction was more common with boosted a protease inhibitor (PI) (9.44%)-based regimen as compared to a non- nucleoside reverse transcriptase inhibitors (NNRTI) (5.01%)-based regimen (P = 0.003). The mean decline in creatinine clearance from baseline was 22.27 ml/min. The median time to develop renal dysfunction was 154 (15-935) days. Serum creatinine returned to normal in all the patients after stopping TDF. Five patients presented with features suggestive of Fanconi's syndrome without alteration in serum creatinine. CONCLUSION: TDF-based treatment is associated with mild but reversible renal dysfunction. Patients receiving PI/r are at a higher risk of renal dysfunction compared to those receiving NNRTI-based ART. Clinicians should be adviced to have intensive renal monitoring, including creatinine clearance, urine examination, K+ and phosphate levels at baseline and during treatment with TDF.

Effectiveness of generic fixed-dose combinations of highly active antiretroviral therapy for treatment of HIV infection in India.

OBJECTIVE: To assess clinical and immunologic effectiveness and acute toxicity to nevirapine (NVP)-based fixed-dose combinations (FDCs) in antiretroviral-naive HIV-1-infected patients in India. DESIGN: Observational study of patients initiated on NVP-based combination therapy delivered as FDCs. METHODS: Antiretroviral-naive HIV-1-infected patients initiated on FDCs (zidovudine/lamivudine [3TC]/NVP or stavudine/3TC/NVP) were assessed clinically and with CD4 counts periodically. Adverse events to NVP were assessed clinically and by laboratory markers. Frequency and risk factors for development of adverse events and clinical outcomes were determined. RESULTS: Of the 1291 patients started on therapy, 1253 completed a minimum of 3 months of follow-up. Rash and hepatitis were documented in 6.6% (95% confidence interval [CI]: 5.5-8.3) and 3.2% (95% CI: 2.3-4.8) of patients initiating therapy, respectively. There was significant improvement in CD4 counts over 2 years. Fourty-eight patients died, and 186 clinical events were documented in these patients. Tuberculosis was the most common cause of morbidity and mortality. Self-reported adherence was high. CONCLUSION: Fixed-dose formulations of NVP-based combination therapy are safe and produced durable clinical and immunologic benefit.