• Adherence to antiretroviral therapy in patients enrolled in a comprehensive care program in Cambodia: a 24-month follow-up assessment

      Spire, Bruno; Carrieri, Patrizia; Sopha, Pal; Protopopescu, Camelia; Prak, Narom; Quillet, Catherine; Ngeth, Chanchhaya; Ferradini, Laurent; Delfraissy, Jean-François; Laureillard, Didier; et al. (2008-05)
      BACKGROUND: The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence. METHODS: Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence. RESULTS: A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence. CONCLUSIONS: At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members.
    • Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

      Janssens, B; Raleigh, B; Soeung, S; Akao, K; Te, V; Gupta, J; Vun, M; Ford, N; Nouhin, J; Nerrienet, E; et al. (2007-11)
      OBJECTIVE: Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS: Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS: Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS: This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.
    • How labour intensive is a doctor-based delivery model for antiretroviral treatment (ART)? Evidence from an observational study in Siem Reap, Cambodia

      Van Damme, W; Kheang, S; Janssens, B; Kober, K; Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium. Médecins Sans Frontières–Belgium, Phnom Penh, Cambodia. (BioMed Central, 2007-05-01)
      BACKGROUND: Funding for scaling-up antiretroviral treatment (ART) in low-income countries has increased substantially, but the lack of human resources for health (HRH) is increasingly being identified as an important constraint for scaling-up ART. METHODS: In a clinic run by Médecins Sans Frontières in Siem Reap, Cambodia, we documented the use of doctor-time for ART in September 2004 and in August 2005, for different phases in ART (pre-ART, ART initiation, ART follow-up Year 1, & ART follow-up Year 2). Based on these observations and using a variety of assumptions for survival of patients on ART (between 90 and 95% annually) and for further reductions in doctor-time per patient (between 0 and 10% annually), we estimated the need for doctors for the period 2004 till 2013 in the Siem Reap clinic, and in a hypothetical district in sub-Saharan Africa. RESULTS: In the Siem Reap clinic, we found that from 2004 to 2005 the doctor-time needed per patient was reduced by between 14% and 33%, thanks to a reduction in number of visits per patient and shorter consultation times. In 2004, 2.06 full-time equivalent (FTE) doctors were needed for 522 patients on ART, and in 2005 this was slightly reduced to 1.97 FTE doctors for 911 patients on ART. By 2013, Siem Reap clinic will need between 2 and 5 FTE doctors for ART. In a district in sub-Saharan Africa with 200,000 inhabitants and 20% adult HIV prevalence, using a similar doctor-based ART delivery model, between 4 and 11 FTE doctors would be needed to cover 50% of ART needs. CONCLUSION: ART is labour intensive. Important reductions in doctor-time per patient can be realized during scaling-up. The doctor-based ART delivery model analysed seems adequate for Cambodia. However, for many districts in sub-Saharan Africa a doctor-based ART delivery model may be incompatible with their HRH constraints.
    • Immunovirological outcomes and resistance patterns at 4 years of antiretroviral therapy use in HIV-infected patients in Cambodia

      Pujades-Rodríguez, Mar; Schramm, Birgit; Som, Leakena; Nerrienet, Eric; Narom, Prak; Chanchhaya, Ngeth; Ferradini, Laurent; Balkan, Suna; Epicentre, Paris, France; Medecins Sans Frontieres, Phnom Penh, Cambodia; HIV⁄Hepatitis Laboratory, Pasteur Institute, Phnom Penh, Cambodia; Khmero-Sovietic Friendship Hospital, Phnom Penh, Cambodia; Medecins Sans Frontieres, Paris, France (2011-02-01)
      Objectives  To report immunovirological outcomes and resistance patterns in adults treated with triple combination antiretroviral therapy (cART) for 4 years in an HIV programme of Phnom Penh, Cambodia. Methods  It is a longitudinal study and cross-sectional evaluation of adults receiving cART for 4 years. CD4 cell counts and HIV-1 RNA were quantified, and resistance patterns were determined. Drug-related toxicity was assessed by clinicians and through laboratory testing. Results  After 4 years of cART start, the cumulative probability of retention in care was 0.80 and survival among patients not lost to follow-up was 0.85. A total of 349 patients (98% of eligible) participated in the cross-sectional evaluation. Ninety per cent were receiving first-line therapy, 29% stavudine- and 58% zidovudine-containing regimens (compared with 94% and 3% at cART initiation). Ninety-three per cent of patients were clinically asymptomatic, and severe lipodystrophy and dyslipidemia were diagnosed in 7.2% and 4.0%, respectively. Good treatment adherence was reported by 83% of patients. Median CD4 T-cell count was 410 cells/μl [IQR 290-511], and 90% of patients had >200 cells/μl. Only 15 (4%) patients had detectable HIV viral load (eight had <200 CD4 cells/μl), five had thymidine analogue mutations, and nine were resistant to two drug classes. In an intention-to-treat analysis, 26.1% (95% CI 22.0-30.5) of patients had failed first-line therapy. Conclusions  In this Cambodian cohort of adults who started cART at an advanced stage of HIV disease, we observed good clinical and immunovirological outcomes and self-reported treatment adherence at 4 years of therapy.
    • [Management of HIV/AIDS patients in Kompong Cham, Cambodia]

      Allemand-Sourrieu, J; Gazin, P; Moreau, J; Programme MSF-France de traitement du sida au Cambodge. allemandjulie@yahoo.fr (2007-02)
      In 2003 the NGO Médecins sans Frontières started an anti-viral drug treatment program for HIV/AIDS patients in the regional hospital of Kompong Cham, Cambodia. In 2005 a total of 1100 adults and 149 children were on the active list. Sixty percent of new patients were at WHO stages 3 or 4. Compliance with HAART was high after 24 months. Access to second-line regimens is discussed.
    • Offering Integrated Care for HIV/AIDS, Diabetes and Hypertension within Chronic Disease Clinics in Cambodia.

      Janssens, B; Van Damme, W; Raleigh, B; Gupta, J; Khem, S; Soy Ty, K; Vun, M; Ford, N; Zachariah, R; Médecins Sans Frontières, Phnom Penh, Cambodia. b.janssens@bigfoot.com (WHO, 2007-11)
      PROBLEM: In Cambodia, care for people with HIV/AIDS (prevalence 1.9%) is expanding, but care for people with type II diabetes (prevalence 5-10%), arterial hypertension and other treatable chronic diseases remains very limited. APPROACH: We describe the experience and outcomes of offering integrated care for HIV/AIDS, diabetes and hypertension within the setting of chronic disease clinics. LOCAL SETTING: Chronic disease clinics were set up in the provincial referral hospitals of Siem Reap and Takeo, 2 provincial capitals in Cambodia. RELEVANT CHANGES: At 24 months of care, 87.7% of all HIV/AIDS patients were alive and in active follow-up. For diabetes patients, this proportion was 71%. Of the HIV/AIDS patients, 9.3% had died and 3% were lost to follow-up, while for diabetes this included 3 (0.1%) deaths and 28.9% lost to follow-up. Of all diabetes patients who stayed more than 3 months in the cohort, 90% were still in follow-up at 24 months. LESSONS LEARNED: Over the first three years, the chronic disease clinics have demonstrated the feasibility of integrating care for HIV/AIDS with non-communicable chronic diseases in Cambodia. Adherence support strategies proved to be complementary, resulting in good outcomes. Services were well accepted by patients, and this has had a positive effect on HIV/AIDS-related stigma. This experience shows how care for HIV/AIDS patients can act as an impetus to tackle other common chronic diseases.
    • Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007)

      Micol, Romain; Buchy, Philippe; Guerrier, Gilles; Duong, Veasna; Ferradini, Laurent; Dousset, Jean-Philippe; Guerin, Philippe J; Balkan, Suna; Galimand, Julie; Chanroeun, Hak; et al. (2009-08-01)
      BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality.
    • Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia.

      Madec, Y; Laureillard, D; Pinoges, L; Fernandez, M; Prak, N; Ngeth, C; Moeung, S; Song, S; Balkan, S; Ferradini, L; et al. (2007-01-30)
      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/microl. 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 < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl 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/microl, patients with CD4 cell count < or = 20 cells/microl 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.
    • Screening and treating cervical cancer in HIV-positive women in Cambodia.

      Raguenaud, Marie-Eve; Isaakidis, Petros; Ping, Chutema; Reid, Tony (2009-08-15)
    • Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries

      Madec, Yoann; Szumilin, Elisabeth; Genevier, Christine; Ferradini, Laurent; Balkan, Suna; Pujades, Mar; Fontanet, Arnaud; Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France; Medecins Sans Frontieres, Paris, France; Medecins Sans Frontieres, Nairobi, Kenya; Infectious Diseases Department, Khmero-Soviet Friendship Hospital, Phnom Penh, Cambodia; Epicentre, Paris, France (2009-04-27)
      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%.