From research to practice: the example of antenatal care in Thailand.

The rationale for providing antenatal care is to screen predominantly healthy pregnant women to detect early signs of, or risk factors for, abnormal conditions or diseases and to follow this detection with effective and timely intervention. The recommended antenatal care programme in most developing countries is often the same as the programmes used in developed countries. However, in developing countries there is wide variation in the proportion of women who receive antenatal care. The WHO randomized trial of antenatal care and the WHO systematic review indicated that a model of care that provided fewer antenatal visits could be introduced into clinical practice without causing adverse consequences to the woman or the fetus. This new model of antenatal care is being implemented in Thailand. Action has been required at all levels of the health-care system, from consumers through to health professionals, the Ministry of Public Health and international organizations. The Thai experience is a good example of moving research findings into practice, and it should be replicated elsewhere to effectively manage other health problems

Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine.

BACKGROUND: Intrapartum single-dose nevirapine plus third trimester maternal and infant zidovudine are essential components of programs to prevent mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings. The persistence of nevirapine in the plasma for 3 weeks postpartum risks selection of resistance mutations to nonnucleoside reverse-transcriptase inhibitors (NNRTIs). We hypothesized that a 1-month zidovudine-didanosine course initiated at the same time as single-dose nevirapine (sdNVP) would prevent the selection of nevirapine-resistance mutations. METHODS: HIV-infected pregnant women in the PHPT-4 cohort with CD4 cell counts >250 cells/mm3 received antepartum zidovudine from the third trimester until delivery, sdNVP during labor, and a 1-month zidovudine-didanosine course after delivery. These women were matched on the basis of baseline HIV load, CD4 cell count, and duration of antepartum zidovudine to women who received sdNVP in the PHPT-2 trial (control subjects). Consensus sequencing and the more sensitive oligonucleotide ligation assay were performed on samples obtained on postpartum days 7-10, 37-45, and 120 (if the HIV load was >500 copies/mL) to detect K103N/Y181C/G190A mutations. RESULTS: The 222 PHPT-4 subjects did not differ from matched control subjects in baseline characteristics except for age. The combined group median CD4 cell count was 421 cells/mm3 (interquartile range [IQR], 322-549 cells/mm3), the median HIV load was 3.45 log10 copies/mL (IQR, 2.79-4.00 log10 copies/mL), and the median duration of zidovudine prophylaxis was 10.4 weeks (IQR, 9.1-11.4 weeks). Using consensus sequencing, major NNRTI resistance mutations were detected after delivery in 0% of PHPT-4 subjects and 10.4% of PHPT-2 controls. The oligonucleotide ligation assay detected resistance in 1.8% of PHPT-4 subjects and 18.9% of controls. Major NNRTI resistance mutations were detected by either method in 1.8% of PHPT-4 subjects and 20.7% of controls (P < .001). CONCLUSIONS: A 1-month postpartum course of zidovudine plus didanosine prevented the selection of the vast majority of NNRTI resistance mutations

Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

BACKGROUND: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary

Number of primary outcomes by arm.

a<p>Including nine cases followed by death.</p>b<p>Tuberculosis (8), cryptococcal meningitis (3), <i>P. jirovecii</i> pneumonia (2), systemic <i>P. marneffei</i> (2), disseminated <i>Mycobacterium avium intracellulare</i> (1), sepsis (2).</p>c<p>Tuberculosis (4), cryptococcal meningitis (4), <i>P. jirovecii</i> pneumonia (2), systemic <i>P. marneffei</i> (2), sepsis (3).</p>d<p>Sepsis (3), cerebrovascular accidents (2), heart failure (1), asthma attack (1), <i>P. jirovecii</i> pneumonia (1), hepatic failure (1), unknown cause (2).</p>e<p>Heart failure (3), cancer (2, 1 breast cancer, 1 liver cancer), suicide (2), renal failure (1), hepatic failure (1), pneumonia (1), sepsis (1).</p

Characteristics of the patients at baseline, according to randomization arm.

a<p>There were eight protocol deviations reported related to inclusion criteria: One patient was not ARV naive, one woman was pregnant, one was chronically infected with hepatitis C, two had hemoglobin level <8.0 g/dl, two had absolute neutrophil count <1,000 cells/mm³, one had serum creatinine above 1.0× ULN.</p

Treatment switch to second-line, PI-based treatment.

a<p>Calculated starting in the middle of the time period between the last VL <400 copies/ml and first VL above.</p>b<p>Calculated starting in the middle of the time period between the last VL <50 copies/ml and first VL above.</p

Primary outcomes (clinical failure) at 3 y: death, new AIDS-defining events, or confirmed CD4 <50/mm³.

a<p>The 95% CI of the difference, −0.6% was −4.5% to 3.4%. The upper limit of this CI was below the pre-determined criterion for non-inferiority, 7.4%.</p

Serious adverse events by trial arm.

<p>Serious adverse events by trial arm.</p

Risk factors for clinical failure.

a<p>HR, hazard ratio.</p>b<p>Adjusted HR (AHR, Cox proportional analysis) adjusted for hemoglobin, CDC stage, CD4 count, VL, BMI, sex, and randomization arm.</p

Resistance mutations found at first ARV switch (VL arm).

<p>This table shows 18 patients randomized to the VL arm who reached switching criteria of >400 copies/ml. The last samples collected before switch were genotyped. One participant with extensive PI resistance in the pretreatment specimen is omitted from this table.</p>a<p>“Duration of replication before genotype” is defined as time from first detection of VL >400 copies/ml to genotyping. This may be shorter than the duration before ARV drug switching.</p>b<p>These two participants were not included in calculations related to ARV drug switches since, although they met VL criteria for switching during the study, they both switched after the end of the study (April 1, 2010).</p