Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India.

Background: Single dose of Nevirapine to prevent mother to child transmission of HIV is the commonest preventive regimen in resource-limited countries. Objectives: The objective of this study was to detect drug-resistant virus after single dose of Nevirapine (sdNVP) provided to delivering HIV seropositive (HIV+ve) women and to evaluate the time taken for its decay. Results: Of the 36 consenting HIV+ve pregnant women enrolled into the study, the mean hemoglobin and total lymphocyte counts were 10.8 g/dl and 1843 cells/mm 3 , respectively. Mean CD4 counts in 64% of women was 363 cells/mm 3 and mean viral load for 16/36 women was 28,143 copies/ml of plasma. Nevirapine-resistance mutations were detected in 28% of women at delivery; using OLA (Oligonucleotide Ligation Assay). K103N mutations were seen in 19.4% of women while the Y181C mutation was seen in 5%. Both the mutations were detected in 2.7% of women. Sequential blood samples collected at delivery, 7-10 days, 6 weeks, 4 months, 6 months and one year postpartum showed that 81% of K103N mutations and 66.7% of Y181C mutations were detected at 6 weeks postpartum . Wild-type virus had replaced the mutants by one year postpartum in all women except one. Conclusion : These observations are relevant for future treatment with antiretroviral therapy in these women for their HIV disease.

Mother-to-child transmission of HIV among women who chose not to exclusively breastfeed their infants in Pune, India.

BACKGROUND & OBJECTIVE: The percentage of HIV cases attributed to mother-to-child transmission (MTCT) has increased several fold in recent years. No reports are available on HIV MTCT rates among HIV-infected choosing not be exclusively breastfeed their infants in India. We examined HIV MTCT rates among 41 Indian women in a prospective cohort who chose predominantly not to exclusively breastfeed. METHODS: Of the 41 women, 27 (66%) received MTCT prophylaxis: 3 received short course zidovudine (AZT), 19 single-dose nevirapine (NVP), and 5 both AZT and NVP. Maternal HIV-I RNA levels (viral load) were measured at the time of delivery. Infants were tested for HIV-1 infection by PCR up to 11 times is first year of life and viral load was measured in PCR positive infants. RESULTS: All infants received single dose NVP. Thirty two (76%) infants were exclusively formula-fed, 10 (24%) were mixed fed. Four infants were diagnosed with HIV infection for an overall 12- month transmission probability of 8 per cent [95% confidence interval (CI) of 3.2 to 22.1%]. Restricting analysis to 31 women who exclusively formula-fed, only one (3.1%) transmission event occurred. The 41 HIV-infected women gave birth to 42 live-born infants. INTERPRETATION & CONCLUSION: Our data from a small cohort of HIV-infected women suggest that short-course AZT or single dose NVP are effective in reducing MTCT in an Indian setting. Larger studies are needed to assess HIV MTCT rates in India, but in this small study rates were comparable to that observed among women who chose not to exclusively breastfeed in other resource-limited settings.

Fixed dose combination of lamivudine, stavudine and nevirapine in the treatment of pediatric HIV infection: a preliminary report.

To assess efficacy and safety of fixed-dose combination (FDC) of lamivudine, stavudine and nevirapine in the treatment of pediatric HIV- infection, it was administered in the form of oral suspension (Group-A) or dispersible tablet (Group-B). Assessment of improvement in symptoms, CD4 count and adverse drug reactions was done every three months. Baseline CD4 count/mm3 in Group-A (n = 13) patients aged < or =1 yr, 1 to 5 yr and > or = 6 yr increased by 79, 152, 342, 988; 422.8, 514.2, 711.6, 832.6; and 205, 332.7, 516.8, 761.6 after 3, 6, 9 and 12 months of therapy, respectively. The corresponding baseline CD4 count/mm3 in Group-B (n = 8) patients in the three age categories increased by 370, 644.5 and 314 after 3 months, respectively. Improvement in the clinical category was observed in all the patients taking study medication, including weight gain; and decreased incidence of fever, diarrhea, infections and hospitalization. None of the patients had any drug-related adverse effect. Adherence to the regimen was < 95 % and there were no treatment failures.

Antiretroviral therapy in children: Indian experience.

BACKGROUND : There is a paucity of reports on Highly Active Antiretroviral therapy (HAART) in children. We studied feasibility and effectiveness fixed dose combination (FDC) of lamivudine, nevirapine and stavudine in HIV infected children. DESIGN: Interventional study. SETTING: A Tertiary care center. SUBJECTS: Twenty five consecutive HIV positive antiretroviral naive children older than 18 months. METHODS: The study subjects were started on weight-appropriate doses of the FDC and followed up for 6 months. Weight, CD4 counts, absolute lymphocyte count (ALC) and number of episodes of illness were assessed before and after HAART. Adherence and barriers to adherence were studied. RESULTS: Mean weight increased from 15.2 to 16.8 kg (P < 0.001) while mean CD4 counts increased from 488/cmm to 765/cmm (P < 0.001). Only 2 cases of drug associated adverse event were encountered. Improvement in Center for Disease Control (CDC) immunological classification of the subjects was significant while that in World Health Organization (WHO) clinical staging was not statistically significant. Follow up visits were 95% of the expected 175 visits. The average distance traveled by the patient for every visit was 72 km (one way). CONCLUSIONS: Use of FDC in weight specific dosages is feasible and effective for treatment of Pediatric HIV in resource scarce setting. These preliminary results need to be tested in a different setting.

Plasma nevirapine levels and 24-week efficacy of a fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) among Thai HIV-infected patients.

BACKGROUND: A fixed-dose combination of stavudine, lamivudine, and nevirapine (GPO-VIR) is the most affordable antiretroviral therapy (ART) regimen in Thailand. The data of nevirapine (NVP) level and efficacy of this fixed-dose combination is limited. MATERIAL AND METHOD: Patients who were initiated GPO-VIR in 2004 were enrolled NVP levels at 12 weeks were determined. Patients were followed for 24 weeks. RESULTS: Fifty-nine patients with a mean age of 36.4 years and 54% male were enrolled. Mean body weight was 54.7 kgs. Median baseline CD4 and HIV-RNA were 29 cells/mm3 and 270,000 (5.4 log10) copies/mL, respectively. Mean plasma NVP levels at 12 weeks was 6.4 mg/L. By linear regression, female gender (p = 0.042), and higher weight (p = 0.020) were associated with lower NVP levels. At 24 weeks, 78% achieved undetectable HIV-RNA and median CD4 was 156 cells/mm3. CONCLUSION: NVP levels and 24-week efficacy of GPO-VIR are favorable. According to the affordable cost, GPO-VIR should be an appropriate initial regimen for naïve HIV-infected patients in resource-limited settings.

Efficacy of a generic fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) in Thai HIV-infected patients.

BACKGROUND: GPO-VIR, fixed-dose combination of stavudine 30/40 mg, lamivudine 150 mg, and nevirapine 200 mg are widely used in Thailand. OBJECTIVE: Determine the efficacy and tolerability of GPO-VIR in naive HIV-infected patients. MATERIAL AND METHOD: Primary outcome was the time of initiation to achieve the goal of therapy, which was HIV RNA < 50 copies/mL or 50% increased of CD4 cell count. Ninety patients were eligible for the present study. Mean +/- SD age was 35 +/- 7 years and 51% were male. Median baseline CD4 and HIV RNA were 52 cells/ mm3 and 280,000 (5.4 log10) copies/mL, respectively. Sixty-two (69%) patients had previous opportunistic infections. RESULTS: In a median follow-up period of 15 weeks, 49 (54%) patients achieved the goal of therapy. The probability of goal achievement showed that 12-, 24-, 36- and 48- weeks success rates were 8.5% [95% confidence interval (CI): 3.9-18.0%], 62.7% (95% CI: 50.8-74.6%), 80.0% (95% CI: 67.3-90.1%), and 93.3% (95% CI: 76.3-99.4%), respectively. The median success time to achieve the goal was 21 weeks. Eleven (12%) patients needed to discontinue GPO-VIR because of adverse drugs reaction. CONCLUSION: GPO-VIR may be one of the antiretroviral regimens for HIV-infected patients in Thailand and other resource-limited countries. Its efficacy is good in patients with advanced HIV infection.

Efficacy and safety of generic fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-vir) in advanced HIV infection.

OBJECTIVES: To assess the efficacy and safety of generic fixed-dose combination of stavudine, lamivudine and nevirapine; GPO-vir in advanced HIV infection. MATERIAL AND METHOD: Open-label combined prospective and retrospective study involving 102 HIV infected patients with baseline CD4 cell count < 100 cells/mm3. All patients received GPO-vir for 48 weeks. The CD4 cell count and plasma viral load (pVL) was measured at 48 weeks. RESULTS: The median baseline CD4 cell count and pVL were 13 cells/mm3 and 363,500 copies/ml, respectively. At 48 weeks, the median CD4 cell count increased to 191 cells/mm3 and 63.7% in intention-to treat and 82.3% in on-treatment analysis had pVL < 50 copies/ml. There was no significant difference in pVL between patients with baseline pVL > 100,000 or < or = 100,000 copies/ml (p = 0.312). The incidence of hepatotoxicity, rash and peripheral neuropathy was 4.9%, 14.7% and 6.9%, respectively. CONCLUSION: GPO-vir was well tolerated and effective in increasing CD4 cell count and suppressing plasma viremia in advanced HIV infection during the 48 weeks follow-up period.

Urine nevirapine as a predictor of antiretroviral adherence.

BACKGROUND & OBJECTIVE: Incomplete adherence is a major contributor to failure of antiretroviral therapy. Although the available methods to monitor adherence to therapy have proved to be predictive of outcomes, the results are variable. We assessed the feasibility of detecting nevirapine (NVP) in spot urine samples to monitor patient adherence to antiretroviral treatment and to study the urinary excretion of NVP in healthy volunteers after oral administration of a single dose of NVP (200 mg). METHODS: Spot urine samples were collected from 50 HIV-infected patients (36 on treatment regimen containing NVP and 14 on drugs other than NVP) and tested for NVP by HPLC in a blinded manner. Sixteen healthy volunteers (9 males and 7 females) were administered a single oral dose of 200 mg NVP and spot urine samples were collected on day '0' before drug administration, and thereafter every 24 h up to 9 days and tested for NVP. RESULTS: All the urine samples collected from patients undergoing treatment with NVP-containing regimens at different time points after drug administration tested positive for NVP. Thirteen out of 14 samples from patients not on NVP yielded a negative result. The drug was detected in the urine of healthy volunteers up to 9 days. The urinary excretion of NVP was prolonged in females than in males. INTERPRETATION & CONCLUSION: In view of its long half-life, NVP gets excreted in urine for a long period of time. Hence, testing spot urine samples for NVP may not be a useful measure to monitor patient adherence to treatment.

Aplastic anemia in an HIV infected child.

Hematologic manifestations of HIV in children are common and include anemia, neutropenia, lymphocytopenia, thrombocytopenia that may occur due to many reasons. However, aplastic anemia due to HIV infection is rare and even more so in children. Though anemia is seen with advanced disease and associated with poor prognosis it is treated with various therapeutic modalities. Our patient with aplastic anemia due to HIV infection responded to antiretroviral therapy.

HIV seroprevalence, uptake of interventions to reduce mother-to-child transmission and birth outcomes in greater Kingston, Jamaica

BACKGROUND: The seroprevalence of HIV among pregnant women in the Caribbean is 2-3 and increasing. The Kingston Paediatric and Perinatal HIV Programme is developing and implementing a unified programme to eliminate mother-to-child transmission (MTCT) of HIV in Kingston, Jamaica. METHODS: Pregnant women presenting to Kingston Metropolitan Antenatal Clinics, Victoria Jubilee Hospital, Spanish Town Hospital and the University Hospital of the West Indies had HIV serology performed by ELISA, or by the new Determine Rapid Test after receiving group counselling. HIV-positive women were referred to High Risk Antenatal Clinics. Antiretroviral prophylaxis with zidovudine (AZT), or nevirapine was given. Care was administered using a standard protocol by a multi-disciplinary team of public and academic healthcare personnel. RESULTS: In year one, 19,414 women delivered Among 14,054 women who started antenatal care for this period, 5,558 (40) received group counselling and 7,383 (53) received HIV-testing. During the fourth quarter of follow-up, these comparative rates were 66 (2049/3 118) and 72 (2260/3118) respectively. HIV seroprevalence overall was 2.1 (152/7 383). One hundred and seven HIV+ women at varying gestational ages were identified in the programme, 72 had so far received AZT and nine nevirapine (76). 0f 84 deliveries, birth outcomes were 75 live births (89), six neonatal deaths and four maternal deaths (all from HIV/AIDS). Major challenges include repeat pregnancies of 36 despite prior knowledge of HIV seropositivity and poor partner notification with only 30 (32) having a HIV-test. Although rates of HIV testing in pregnant women in Greater Kingston are increasing, rates of testing overall remain sub-optimal. On the labour ward, there was sub-optimal identification of the HIV+ pregnant woman and administration of AZT chemoprophylaxis, along with issues of patient confidentiality and stigma. CONCLUSION: This programme needs strengthening in order to reduce maternal-fetal transmission of HIV in Greater Kingston, Jamaica [quot]pMTCT-PLUS, or comprehensive family-centred care, is the next step[quot]

Safety and efficacy of a simplified fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) for the treatment of advanced HIV-infected patients: a 24-week study.

OBJECTIVE: To determine the efficacy and safety of the fixed-dose combination of stavudine (d4T), lamivudine (3TC) and nevirapine (NVP) in the treatment of antiretroviral naive HIV-infected Thai adults. PATIENTS AND METHOD: An open-label, single arm trial was conducted Baseline clinical assessment and blood test was done on 10, antiretroviral naive HIV-infected patients, who then received a fixed dose combination of d4T, 3TC and NVP (GPO- VIR, Thai Government Pharmaceutical Organization, Bangkok, Thailand). Nevirapine was given as 200 mg once daily for the first 2 weeks. The patients were followed up at 2, 4, 8, 12 and 24 weeks. A CD4 cell count and HIV-RNA assay were done at 12 and 24 weeks. RESULTS: One hundred and one patients were enrolled The mean baseline CD4 cell count and mean HIV RNA were 58.7 (57.7) cells/mm3 and 5.3 (0.5) log10, copies/mL respectively. At week 24th, the mean decrease in log HIV RNA was 3.6 (0.7) log10 copies/mL [P < 0.001; 95% confidence interval (CI), 2.70-3.03]. Eighty one (80.2%) patients had HIV RNA < 400 copies/mL by intention-to-treat analysis (ITT) and 97.6% had HIV RNA < 400 copies/mL by on-treatment analysis (OT). Sixteen (84.2%) patients with baseline HIV RNA < or = 100,000 copies/mL and 65 (82.3%) patients with baseline HIV RNA > 100,000 copies/mL had viral load < 400 copies/mL by ITT (P = 0.842; 95% CI, -20.9%-16.2%). Sixteen (94.1%) patients with baseline HIV RNA < or = 100,000 copies/mL and 65 (98.5%) patients with baseline HIV RNA > 100,000 copies/mL had viral load < 400 copies/mL by OT (P = 0.295; 95% CI, -25.5%-3.8%). The mean CD4 cell count at week 24 was 155.1 (89.0) cells/mm3 (range 13-402). The mean increase in CD4 cell count from baseline was 96.5 (63.5) cells/ mm3 (P < 0.001). A total of 12% of the patients receiving d4T + 3TC + NVP developed skin rashes. Grade 3 or 4 hepatotoxicity was recognized in 7% of the patients. CONCLUSION: Fixed-dose combination of d4T + 3 TC + NVP (GPO- VIR) is safe, well tolerated and effective in increasing CD4 cell counts and suppression of HIV RNA at 24 weeks in advanced HIV-infected patients in Thailand.