HIV viraemia during pregnancy in women receiving preconception antiretroviral therapy in KwaDukuza, KwaZulu-Natal

Background: Preconception antiretroviral therapy (PCART) followed by sustained viral suppression is effective in preventing mother-to-child transmission of HIV. The rates of persistent and transient viraemia in such patients have not been prospectively assessed in South Africa. Objectives: We determined the prevalence of transient and persistent viraemia in HIV-positive women entering antenatal care on PCART and studied variables associated with viraemia. Methods: We performed a prospective cross-sectional observational study of HIV-positive pregnant women presenting to a primary healthcare facility in KwaZulu-Natal. All had received at least 6 months of first-line PCART. Viral load (VL) was measured, patients were interviewed, adherence estimated using a visual analogue scale and adherence counselling provided. Viral load was repeated after 4 weeks where baseline VL exceeded 50 copies/mL. Results: We enrolled 82 participants. Of them, 59 (72%) pregnancies were unplanned. Fifteen participants (18.3%) were viraemic at presentation with VL > 50 copies/mL. Of these, seven (8.5%) had viral suppression (VL < 50 copies/mL), and eight remained viraemic at the second visit. Adherence correlated significantly with viraemia at baseline. Level of knowledge correlated with adherence but not with lack of viral suppression at baseline. Socio-economic indicators did not correlate with viraemia. No instances of vertical transmission were observed at birth. Conclusions: Approximately 20% of women receiving PCART may demonstrate viraemia. Half of these may be transient. Poor adherence is associated with viraemia, and efforts to encourage and monitor adherence are essential. The rate of unplanned pregnancies is high, and antiretroviral therapy programmes should focus on family planning needs of women in the reproductive age group to prevent viral non-suppression prior to pregnancy

Challenges for Routine Health System Data Management in a Large Public Programme to Prevent Mother-to-Child HIV Transmission in South Africa

Background: Recent changes to South Africa's prevention of mother-to-child transmission of HIV (PMTCT) guidelines have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. While programmatic efforts to reach this target are underway, obtaining complete and accurate data from clinical sites to track progress presents a major challenge. We assessed the completeness and accuracy of routine PMTCT data submitted to the district health information system (DHIS) in three districts of Kwazulu-Natal province, South Africa. Methodology/Principal Findings: We surveyed the completeness and accuracy of data reported for six key PMTCT data elements between January and December 2007 from all 316 clinics and hospitals in three districts. Through visits to randomly selected sites, we reconstructed reports for the same six PMTCT data elements from clinic registers and assessed accuracy of the monthly reports previously submitted to the DHIS. Data elements were reported only 50.3% of the time and were “accurate” (i.e. within 10% of reconstructed values) 12.8% of the time. The data element “Antenatal Clients Tested for HIV” was the most accurate data element (i.e. consistent with the reconstructed value) 19.8% of the time, while “HIV PCR testing of baby born to HIV positive mother” was the least accurate with only 5.3% of clinics meeting the definition of accuracy. Conclusions/Significance: Data collected and reported in the public health system across three large, high HIV-prevalence Districts was neither complete nor accurate enough to track process performance or outcomes for PMTCT care. Systematic data evaluation can determine the magnitude of the data reporting failure and guide site-specific improvements in data management. Solutions are currently being developed and tested to improve data quality

The impact of continuous quality improvement on coverage of antenatal HIV care tests in rural South Africa: results of a stepped-wedge cluster-randomised controlled implementation trial

Background: Evidence for the effectiveness of continuous quality improvement (CQI) in resource-poor settings is very limited. We aimed to establish the effects of CQI on quality of antenatal HIV care in primary care clinics in rural South Africa. Methods and findings: We conducted a stepped-wedge cluster-randomised controlled trial (RCT) comparing CQI to usual standard of antenatal care (ANC) in 7 nurse-led, public-sector primary care clinics—combined into 6 clusters—over 8 steps and 19 months. Clusters randomly switched from comparator to intervention on pre-specified dates until all had rolled over to the CQI intervention. Investigators and clusters were blinded to randomisation until 2 weeks prior to each step. The intervention was delivered by trained CQI mentors and included standard CQI tools (process maps, fishbone diagrams, run charts, Plan-Do-Study-Act [PDSA] cycles, and action learning sessions). CQI mentors worked with health workers, including nurses and HIV lay counsellors. The mentors used the standard CQI tools flexibly, tailored to local clinic needs. Health workers were the direct recipients of the intervention, whereas the ultimate beneficiaries were pregnant women attending ANC. Our 2 registered primary endpoints were viral load (VL) monitoring (which is critical for elimination of mother-to-child transmission of HIV [eMTCT] and the health of pregnant women living with HIV) and repeat HIV testing (which is necessary to identify and treat women who seroconvert during pregnancy). All pregnant women who attended their first antenatal visit at one of the 7 study clinics and were ≥18 years old at delivery were eligible for endpoint assessment. We performed intention-to-treat (ITT) analyses using modified Poisson generalised linear mixed effects models. We estimated effect sizes with time-step fixed effects and clinic random effects (Model 1). In separate models, we added a nested random clinic–time step interaction term (Model 2) or individual random effects (Model 3). Between 15 July 2015 and 30 January 2017, 2,160 participants with 13,212 ANC visits (intervention n = 6,877, control n = 6,335) were eligible for ITT analysis. No adverse events were reported. Median age at first booking was 25 years (interquartile range [IQR] 21 to 30), and median parity was 1 (IQR 0 to 2). HIV prevalence was 47% (95% CI 42% to 53%). In Model 1, CQI significantly increased VL monitoring (relative risk [RR] 1.38, 95% CI 1.21 to 1.57, p &lt; 0.001) but did not improve repeat HIV testing (RR 1.00, 95% CI 0.88 to 1.13, p = 0.958). These results remained essentially the same in both Model 2 and Model 3. Limitations of our study include that we did not establish impact beyond the duration of the relatively short study period of 19 months, and that transition steps may have been too short to achieve the full potential impact of the CQI intervention. Conclusions: We found that CQI can be effective at increasing quality of primary care in rural Africa. Policy makers should consider CQI as a routine intervention to boost quality of primary care in rural African communities. Implementation research should accompany future CQI use to elucidate mechanisms of action and to identify factors supporting long-term success. Trial registration: This trial is registered at ClinicalTrials.gov under registration number NCT02626351

Data Accuracy by Data element shown.

<p>Data Accuracy by Data element shown.</p

Figure 2

<p>a, b & c. Completeness of individual PMTCT data elements in all districts (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005483#pone-0005483-g002" target="_blank">Figure 2a</a>), aggregate data completeness by district for all six PMTCT data elements (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005483#pone-0005483-g002" target="_blank">Figure 2b</a>), and aggregated data completeness by facility type for all six PMTCT data elements (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005483#pone-0005483-g002" target="_blank">Figure 2c</a>).</p

Figure 4

<p>a & b: Data concordance between Clinics' Monthly Summary sheets and DHIS report (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005483#pone-0005483-g004" target="_blank">Figure 4a</a>) and between Clinics' register data and Monthly Summary sheet (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005483#pone-0005483-g004" target="_blank">Figure 4b</a>).</p

Missing data and errors according to data element.

<p>Missing data and errors according to data element.</p

Human Immunodeficiency Virus-Specific CD8+ T-Cell Activity Is Detectable from Birth in the Majority of In Utero-Infected Infants▿

Human immunodeficiency virus (HIV)-infected infants in sub-Saharan Africa typically progress to AIDS or death by 2 years of life in the absence of antiretroviral therapy. This rapid progression to HIV disease has been related to immaturity of the adaptive immune response in infants. We screened 740 infants born to HIV-infected mothers and tracked development and specificity of HIV-specific CD8+ T-cell responses in 63 HIV-infected infants identified using gamma interferon enzyme-linked immunospot assays and intracellular cytokine staining. Forty-four in utero-infected and 19 intrapartum-infected infants were compared to 45 chronically infected children >2 years of age. Seventy percent (14 of 20) in utero-infected infants tested within the first week of life demonstrated HIV-specific CD8+ T-cell responses. Gag, Pol, and Nef were the principally targeted regions in chronic pediatric infection. However, Env dominated the overall response in one-third (12/36) of the acutely infected infants, compared to only 2/45 (4%) of chronically infected children (P = 0.00083). Gag-specific CD4+ T-cell responses were minimal to undetectable in the first 6 months of pediatric infection. These data indicate that failure to control HIV replication in in utero-infected infants is not due to an inability to induce responses but instead suggest secondary failure of adaptive immunity in containing this infection. Moreover, the detection of virus-specific CD8+ T-cell responses in the first days of life in most in utero-infected infants is encouraging for HIV vaccine interventions in infants