Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a systematic review and meta-analysis.

INTRODUCTION: Co-trimoxazole prophylaxis is used to reduce morbidity and mortality in people with HIV. We systematically reviewed three topics related to co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation, and dose. METHODS: We searched PubMed, Embase, WHO Global Index Medicus, and clinical trial registries in November, 2013, for randomised controlled trials and observational studies including co-trimoxazole prophylaxis and a comparator group. Studies were eligible if they reported death, WHO clinical stage 3 or 4 events, admittance to hospital, severe bacterial infections, tuberculosis, pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant mortality, low birthweight, and placental malaria were additional outcomes for the comparison of co-trimoxazole prophylaxis and intermittent preventive treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co-trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a 10% margin for non-inferiority and equivalence analyses. We used random-effects models for all meta-analyses. This study is registered with PROSPERO, number CRD42014007163. FINDINGS: 19 articles, published from 1995 to 2014 and including 35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis reduced rates of death (hazard ratio [HR] 0·40, 95% CI 0·26-0·64) when started at CD4 counts of 350 cells per µL or lower with antiretroviral therapy (ART) worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per µL without ART reduced rates of death (0·50, 0·30-0·83) and malaria (0·25, 0·10-0·57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect to infant mortality (risk difference [RD] -0·05, 95% CI -0·12 to 0·02), low birthweight (0·00, -0·07 to 0·07), and placental malaria (0·00, -0·10 to 0·10). Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4 counts higher than 350 cells per µL reduced admittances to hospital (HR 0·42, 95% CI 0·22-0·80), pneumonia (0·73, 0·61-0·88), malaria (0·03, 0·01-0·10), and diarrhoea (0·61, 0·48-0·78) in Africa. A dose of 480 mg co-trimoxazole prophylaxis once a day did not reduce treatment-limiting adverse events compared with 960 mg once a day (RD -0·07, 95% CI -0·52 to 0·39). INTERPRETATION: Co-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per µL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings. FUNDING: None.

Adoption of national recommendations related to use of antiretroviral therapy before and shortly following the launch of the 2013 WHO consolidated guidelines.

OBJECTIVE: To determine the status of key national policies on the use of antiretroviral therapy (ART) at the time of the launch of the 2013 WHO consolidated guidelines as well as to track early progress towards adoption of these recommendations following dissemination. DESIGN: Descriptive analysis of global data on baseline ART policies as of June 2013 and early intentions to adopt the 2013 WHO for use of antiretroviral drugs guidelines as of November 2013. METHODS: Compilation of existing global reports on key HIV policies, review of national guidelines, data collection through annual drug procurement surveys and through guidelines dissemination meetings in each of the six WHO regions. RESULTS: Data were available from 124 low- and middle-income countries, including 97% of the 57 high-priority countries that have been identified by WHO and the Joint United Nations Program on HIV/AIDS (UNAIDS). At baseline, only one country reported recommending antiretroviral therapy (ART) at a CD4 T-cell count 250 cells/µl or less for adults and adolescents in 2013, whereas nine countries already recommended using CD4 T-cell count 500 cells/µl or less. Recommendations for ART initiation regardless of CD4 T-cell count for HIV-infected patients with tuberculosis (86%), hepatitis B (75%), all HIV-infected women who were pregnant or breastfeeding (option B+: 40%) or HIV-infected persons in a serodiscordant relationship (26%) had been nationally adopted as of June 2013. Eight of 67 countries (12%) already recommended treating all children less than 5 years of age. The triple antiretroviral combination of tenofovir + lamivudine (or emtricitabine) + efavirenz was recommended as the preferred first-line option for adults and adolescents more frequently (51%) than for pregnant women (38%), or for both adults/adolescents and pregnant women (28%; P < 0.05). Fewer than half (37%) of all countries reported recommending lopinavir/ritonavir for all HIV-infected children less than 3 years of age; 54% of countries reported recommending routine viral load monitoring, whereas only 41% recommended nurse-initiated ART. CONCLUSIONS: A number of key WHO policy recommendations on antiretroviral drug use were adopted rapidly by countries in advance of or shortly following the launch of the 2013 guidelines. Efforts are needed to support and track ongoing policy adoption and ensure that it is accompanied by the scale-up of evidence-based interventions.

Changing mortality profile among HIV-infected patients in Rio de Janeiro, Brazil: shifting from AIDS to non-AIDS related conditions in the HAART era.

INTRODUCTION: We describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ). METHODS: Adult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients' medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling. RESULTS: A total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7-9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986-1991 to 1.35/100PYs in 2007-2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause. CONCLUSIONS: Our results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.

Trends in retention on antiretroviral therapy in national programs in low-income and middle-income countries.

OBJECTIVES: To document regional and global trends for patients retained on antiretroviral therapy (ART) 12-48 months after treatment initiation, in low-income and middle-income countries. METHODS: Data reported by national programs to WHO/UNICEF/UNAIDS in 2008 were aggregated to produce regional and global estimates. The proportion of patients on ART at 12, 24, 36, and 48 months is derived from cohort monitoring systems in ART dispensing facilities. RESULTS: Of 149 countries, 70 (47%) reported on retention at 12 months, 54 (36%) at 24 months, 38 (26%) at 36 months, and 30 (20%) at 48 months. Regional and global trends showed that the majority of attrition from ART programs occurred within the first year and declined thereafter. Among countries in sub-Saharan Africa, retention on ART was estimated at 75.2% at 12 months, 66.8% at 24 months, and remained at a similar level up to 48 months. CONCLUSIONS: After high attrition in the first year, retention on ART tends to stabilize. In the literature, attrition in the first year was related to early mortality. Earlier presentation for diagnosis of HIV infection, timely screening, and access to ART are fundamental to reduce it. Countries need support in reporting on outcomes on ART.