Fixed-dose Combination Of Stavudine Research Articles

Antiretroviral treatment uptake and attrition among HIV-positive patients with tuberculosis in Kibera, Kenya

Using data of human immunodeficiency virus-positive patients with tuberculosis from three primary care clinics in Kibera slums, Nairobi, Kenya, we report on the proportion that started antiretroviral treatment (ART) and attrition (deaths, lost to follow-up and stopped treatment) before and while on ART. Of 427 ART eligible patients, enrolled between January 2004 and December 2008, 70% started ART, 19% were lost to attrition and 11% had not initiated ART. Of those who started ART, 14% were lost to attrition, making a cumulative pre-ART and ART attrition of 33%. ART uptake among patients with TB was relatively good, but programme attrition was high and needs urgent addressing.

Reversible Reduction of Nevirapine Plasma Concentrations During Rifampicin Treatment in Patients Coinfected With HIV-1 and Tuberculosis

Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. HIV-1-infected patients with CD4+ T-lymphocyte count <or=100 cells per microliter and TB diagnosis received standard anti-TB therapy and a fixed-dose combination of stavudine, lamivudine, and NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy. In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 microg x mL(-1) x h(-1); P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 microg x mL(-1) x h(-1); P = 0.17). The median C trough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 microg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 microg/mL; P = 0.17). The proportion of subjects with C trough values <or=3 microg/mL was 31.2% (5 of 16), 40.0% (6 of 15), and 7.7% (1 of 13) at T1, T2, and T3, respectively. The reduction of the area under the curve of NVP during concomitant RFM treatment substantially decreases over time.

Efavirenz replacement by immediate full‐dose nevirapine is safe in HIV‐1‐infected patients in Cambodia

Efavirenz is used for the antiretroviral treatment of HIV/tuberculosis-coinfected patients in developing countries. A switch to nevirapine is regularly carried out because of the cost and side effects of efavirenz. Pharmacokinetic studies suggested that nevirapine should be initiated at full dose when used as a substitute for efavirenz. The aim of this study was to measure the cumulative incidence of adverse events (AEs) related to nevirapine in patients switched from efavirenz to immediate full-dose nevirapine (FDN). In 2001 an antiretroviral treatment programme was initiated with the first-line regimen stavudine, lamivudine and efavirenz. In 2003, the fixed-dose combination of stavudine, lamivudine and nevirapine was recommended. Thus, first-line therapy was changed and FDN was initiated when patients were switched from efavirenz to nevirapine. Between April and December 2004, 394 patients were switched from efavirenz to FDN. The cumulative incidence of AEs related to nevirapine was 13.2% [95% confidence interval (CI) 10.2-16.7] and that of severe AEs was 8.9% (95% CI 6.5-11.9). In women the incidence of AEs was 17.6% (95% CI 12.1-24.3) and that of severe AEs was 12.2% (95% CI 7.7-18.2). Our results indicate that an FDN switch from efavirenz does not appear to result in more AEs than when nevirapine is initiated with escalating doses. These data are particularly relevant in resource-limited settings.

Letter to the Editor:Tenofovir Resistance among HIV-Infected Patients Failing a Fixed-Dose Combination of Stavudine, Lamivudine, and Nevirapine in a Resource-Limited Setting

fixed-dose combination of stavudine/lamivudine/nevirapine (d4T/3TC/NVP) is extensively used in developing countries because it is the most accessible antiretroviral therapy (ART). In resource-limited settings the majority of patients for whom this initial ART regimen failed cannot afford resistance testing. Protease inhibitor (PI)-based regimens are commonly used as the second ART regimen in this population. The choice of nucleoside reverse transcriptase inhibitors (NRTIs) as the backbone in the second ART regimen is primarily based on the history of ART experience when resistance testing is not available. However the options for NRTI as the backbone are limited by NRTI cross resistance and the cost of abacavir and didanosine. In a multicenter study of Asian patients nearly 40% who stop d4T/3TC/NVP cannot afford the next regimen. Tenofovir is expected to be available in Thailand and other developing countries in Asia in early 2007 at a low cost. For a large number of patients for whom a fixed-dose combination of d4T/3TC/NVP failed their physicians plan to use tenofovir in the second regimen. Some mutation patterns after failure of d4T/3TC/NVP regimen may limit the use of tenofovir in this setting. (excerpt)

Antiretroviral therapy for children in the routine setting in Malawi

Malawi is scaling up antiretroviral therapy (ART) for HIV-infected patients. Using a fixed-dose combination of stavudine+lamivudine+nevirapine ('Triomune') as the first-line regimen, split tablets are given to children with doses according to body weight. By March 2006, a total of 46 702 patients had been started on ART, of whom 2718 (5.8%) were children aged <15 years. In a subset of 935 children, comprising 486 boys and 449 girls, 1.5% were aged <1 year, 26% were aged 1-4 years, 39% were aged 5-9 years and 33% were aged 10-14 years. Between July and September 2005, 7905 patients started ART, comprising 7469 adults and 436 children. Six-month cohort outcomes censored on 31 March 2006 showed significantly more children alive and significantly fewer children dead or defaulted compared with adults. Between January and March 2005, 4580 patients started ART, comprising 4347 adults and 233 children. Twelve-month cohort outcomes censored on 31 March 2006 showed significantly more children alive compared with adults. The results of this national study should encourage other programmes to invest in ART for children and particularly to monitor their treatment outcomes.

Options for a Second-Line Antiretroviral Regimen for HIV Type 1-Infected Patients Whose Initial Regimen of a Fixed-Dose Combination of Stavudine, Lamivudine, and Nevirapine Fails

A fixed-dose combination of stavudine, lamivudine, and nevirapine is extensively used as an antiretroviral regimen in developing countries because of its affordability. Virological failure with this regimen has become more common, and a second-line regimen needs to be prepared in the national program. Genotypic resistance testing was conducted among human immunodeficiency virus type 1 (HIV-1)-infected patients who experienced treatment failure with their first antiretroviral regimen (a fixed-dose combination of stavudine, lamivudine, and nevirapine) during 2003-2005. Patterns of resistance mutations and options for a second-line regimen were studied. We studied 98 patients (mean age, 35.2 years), of whom, 63% were male. The median duration of antiretroviral therapy was 20 months. The median HIV-1 RNA load at the time of virological failure detection was 4.1 log copies/mL. The prevalences of patients with > or =1 major mutation conferring drug resistance to nucleoside reverse-transcriptase inhibitors and nonnucleoside reverse-transcriptase inhibitors were 95% and 92%, respectively. M184V was the most common nucleoside reverse-transcriptase inhibitor resistance mutation (observed in 89% of patients). Thymidine analogue mutations, K65R, and Q151M were observed in 37%, 6%, and 8% of patients, respectively. Patients with an HIV-1 RNA load of >4 log copies/mL at the time of treatment failure had higher prevalence of thymidine analogue mutations (P=.041), K65R (P=.031), and Q151M (P=.008) mutations. The second-line regimen was determined in a resource-limited setting where tenofovir and enfuvirtide are not available; the options were limited for 48% of patients. After experiencing treatment failure with a fixed-dose combination of stavudine, lamivudine, and nevirapine, almost all patients have lamivudine and nonnucleoside reverse-transcriptase inhibitor resistance. The options for a second-line regimen are limited for one-half of these patients. In resource-limited settings where availability of antiretroviral agents is limited, strategies for prevention of HIV-1 resistance are crucial. Early detection of virological failure may provide more options and better treatment outcomes.

HIV in South East Asia

Abstract The state of the HIV epidemic varies between countries in South East Asia. Thailand, Cambodia and Myanmar are worst affected, with a prevalence of more than 1%. Indonesia and Viet Nam are seeing emerging epidemics in high-risk groups. Most clinical aspects of HIV disease in Asia are similar to the West. Tuberculosis (TB) is the most common opportunistic infection; cryptococcal meningitis is more common than the West, whereas Kaposi's sarcoma is rare. The viral subtypes seen in South East Asia (predominanatly CRF01_AE) appear to respond well to antiretroviral therapy, as does suptype B, and drug toxicity is similar in profile to that seen in the West. Access to treatment is the main problem, but with decreasing drug costs (because of manufacture of generic drugs) and increased national and international funding, access is improving steadily. A fixed-dose combination of stavudine, lamivudine and nevirapine is widely used, but second-line options are limited if this regimen fails. The expense of CD4 testing presents another important barrier to the delivery of effective HIV care. Treatment of TB and HIV co-infection presents a common management problem, because of drug interactions and overlapping toxicity.