Suna Balkan

Positive outcomes of HAART at 24 months in HIV-infected patients in Cambodia

Objectives:African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-poor settings. The long-term virological outcome and clinico-immunological criteria of success remain important questions. We report the outcomes at 24 months of antiretroviral therapy (ART) in patients treated in a Médecins Sans Frontières/Ministry of Health programme in Cambodia. Methods:Adults who started HAART 24 ± 2 months ago were included. Plasma HIV-RNA levels were assessed by real-time polymerase chain reaction. Factors associated with virological failure were analysed using logistic regression. Results:Of 416 patients, 59.2% were men; the median age was 33.6 years. At baseline, 95.2% were ART naive, 48.9% were at WHO stage IV, and 41.6% had a body mass index less than 18 kg/m2. The median CD4 cell count was 11 cells/μl. A stavudine–lamivudine–efavirenz-containing regimen was initiated predominantly (81.0%). At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53 (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to follow-up. Estimates of survival were 85.5% at 24 months. Of 346 tested patients, 259 (74.1%) had CD4 cell counts greater than 200 cells/μl and 306 (88.4%) had viral loads of less than 400 copies/ml. Factors associated with virological failure at 24 months were non-antiretroviral naive, an insufficient CD4 cell gain of less than 350 cells/μl or a low trough plasma ART concentration. In an intention-to-treat analysis, 73.6% of patients were successfully treated. Conclusion:Positive results after 2 years of advanced HIV further demonstrate the efficacy of HAART in the medium term in resource-limited settings.

Treatment Failure and Mortality Factors in Patients Receiving Second-Line HIV Therapy in Resource-Limited Countries

CONTEXT Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. OBJECTIVES To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. DESIGN, SETTING, AND PARTICIPANTS Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. MAIN OUTCOME MEASURES Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. RESULTS The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. CONCLUSIONS Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.

Adherence to the combination of sulphadoxine-pyrimethamine and artesunate in the Maheba refugee settlement Zambia.

Artemisinin‐based combination therapy (ACT) is one strategy recommended to increase cure rates in malaria and to contain resistance to Plasmodium falciparum. In the Maheba refugee settlement, children aged 5 years or younger with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulphadoxine–pyrimethamine (1 day) and artesunate (3 days). To measure treatment adherence, home visits were carried out the day after the last treatment dose. Patients who had any treatment dose left were considered certainly non‐adherent. Other patients’ classification was based on the answers to the questionnaire: patients whose caretakers stated the child had received the treatment regimen exactly as prescribed were considered probably adherent; all other patients were considered probably non‐adherent. Reasons for non‐adherence were assessed. We found 21.2% (95% CI [15.0–28.4]) of the patients to be certainly non‐adherent, 39.4% (95% CI [31.6–47.6]) probably non‐adherent, and 39.4% (95% CI [31.6–47.6]) probably adherent. Insufficient explanation by the dispenser was identified as an important reason for non‐adherence. When considering the use of ACT, the issue of patient adherence remains challenging. However, it should not be used as an argument against the introduction of ACT. For these treatment regimens to remain efficacious on a long‐term basis, specific and locally adapted strategies need to be implemented to ensure completion of the treatment.

Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia.

Background:HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients. Methods:Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively. Results:From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6–78) cells/μl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51–100, 21–50 and ≤ 20 cells/μl, respectively; P < 10−4). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained ≤ 200 and ≤ 100 cells/μl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/μl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05–0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52–0.98). Similar efficacy was found between the stavudine–lamivudine–nevirapine fixed dose combination and the combination stavudine–lamivudine–efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index. Conclusion:Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/μl, patients with CD4 cell count ≤ 20 cells/μl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.

Operational response to malaria epidemics: are rapid diagnostic tests cost-effective?

Objective  To compare the cost‐effectiveness of malaria treatment based on presumptive diagnosis with that of malaria treatment based on rapid diagnostic tests (RDTs).

Evaluation of a 5-year Programme to Prevent Mother-to-child Transmission of HIV Infection in Northern Uganda

Prevention of mother-to-child transmission (PMTCT) is essential in HIV/AIDS control. We analysed 2000-05 data from mother-infant pairs in our PMTCT programme in rural Uganda, examining programme utilization and outcomes, HIV transmission rates and predictors of death or loss to follow-up (LFU). Out of 19,017 women, 1,037 (5.5%) attending antenatal care services tested HIV positive. Of these, 517 (50%) enrolled in the PMTCT programme and gave birth to 567 infants. Before tracing, 303 (53%) mother-infant pairs were LFU. Reasons for dropout were infant death and lack of understanding of importance of follow-up. Risk of death or LFU was higher among infants with no or incomplete intrapartum prophylaxis (OR = 1.90, 95% CI 1.07-3.36) and of weaning age <6 months (OR 2.55, 95% CI 1.42-4.58), and lower in infants with diagnosed acute illness (OR 0.30, 95% CI 0.16-0.55). Mother-to-child HIV cumulative transmission rate was 8.3%, and 15.5% when HIV-related deaths were considered. Improved tracking of HIV-exposed infants is needed in PMTCT programmes where access to early infant diagnosis is still limited.

Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

BackgroundLittle is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice.MethodsCross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/ml) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression.ResultsAt 12 and 24 months of ART, 72% (n = 701) and 70% (n = 369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/ml). Risk factors for virological failure (>1,000 copies/ml) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations.ConclusionEfforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.

Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries.

BACKGROUND In developing countries, access to laboratory tests remains limited, and the use of simple tools such as weight to monitor HIV-infected patients treated with antiretroviral therapy should be evaluated. METHODS Cohort study of 2451 Cambodian and 2618 Kenyan adults who initiated antiretroviral therapy between 2001 and 2007. The prognostic value of weight gain at 3 months of antiretroviral therapy on 3-6 months mortality, and at 6 months on 6-12 months mortality, was investigated using Poisson regression. RESULTS Mortality rates [95% confidence interval (CI)] between 3 and 6 months of antiretroviral therapy were 9.9 (7.6-12.7) and 13.5 (11.0-16.7) per 100 person-years in Cambodia and Kenya, respectively. At 3 months, among patients with initial body mass index less than or equal to 18.5 kg/m (43% of the study population), mortality rate ratios (95% CI) were 6.3 (3.0-13.1) and 3.4 (1.4-8.3) for those with weight gain less than or equal to 5 and 5-10%, respectively, compared with those with weight gain of more than 10%. At 6 months, weight gain was also predictive of subsequent mortality: mortality rate ratio (95% CI) was 7.3 (4.0-13.3) for those with weight gain less than or equal to 5% compared with those with weight gain of more than 10%. CONCLUSION Weight gain at 3 months is strongly associated with survival. Poor compliance or undiagnosed opportunistic infections should be investigated in patients with initial body mass index less than or equal to 18.5 and achieving weight gain less than or equal to 10%.

Malaria Epidemics and Interventions, Kenya, Burundi, Southern Sudan, and Ethiopia, 1999-2004

Effectiveness was reduced by delays and other factors.

Cost-Effectiveness of Primary Prophylaxis of AIDS Associated Cryptococcosis in Cambodia

Background Cryptococcal infection is a frequent cause of mortality in Cambodian HIV-infected patients with CD4+ count ≤100 cells/µl. This study assessed the cost-effectiveness of three strategies for cryptococcosis prevention in HIV-infected patients. Methods A Markov decision tree was used to compare the following strategies at the time of HIV diagnosis: no intervention, one time systematic serum cryptococcal antigen (CRAG) screening and treatment of positive patients, and systematic primary prophylaxis with fluconazole. The trajectory of a hypothetical cohort of HIV-infected patients with CD4+ count ≤100 cells/µl initiating care was simulated over a 1-year period (cotrimoxazole initiation at enrollment; antiretroviral therapy within 3 months). Natural history and cost data (US