Pravi Moodley

Operational effectiveness and 36 week HIV-free survival in the South African programme to prevent mother-to-child transmission of HIV-1

Objective:Previous studies on the operational effectiveness of programmes to reduce transmission of HIV from mother-to-child (PMTCT) in Africa have generally been hospital-based pilot studies with short follow-up periods. Method:Prospective cohort study to evaluate the routine operational effectiveness of the South African National PMTCT Programme, primarily measured by HIV-free survival at 36 weeks post-delivery. Three of eighteen pilot sites participating in the programme were selected as they reflected differences in circumstances, such as HIV prevalence, socioeconomic status and rural–urban location. A total of 665 HIV-positive mothers and their infants were followed. Results:HIV-free survival at 36 weeks varied significantly across sites with 84% in Paarl, 74% in Umlazi and 65% in Rietvlei (P = 0.0003). Maternal viral load was the single most important factor associated with HIV transmission or death [hazard ratio (HR), 1.54; 95% confidence interval (CI), 1.21–1.95]. Adjusting for health system variables (fewer than four antenatal visits and no antenatal syphilis test) explained the difference between Rietvlei and Paarl (crude HR, 2.27; 95% CI, 1.36–3.77; adjusted HR, 1.81; 95% CI, 0.93–3.50). Exposure to breastmilk feeding explained the difference between Umlazi and Paarl (crude HR, 1.74; 95% CI, 1.06–2.84; adjusted HR, 1.41; 95% CI, 0.81–2.48). Conclusion:Ever breastfeeding and underlying inequities in healthcare quality within South Africa are predictors of PMTCT programme performance and will need to be addressed to optimize PMTCT effectiveness.

Incident HIV Infection in Pregnant and Lactating Women and Its Effect on Mother-to-Child Transmission in South Africa

We described HIV incidence and mother-to-child transmission (MTCT) among women during pregnancy and lactation. Forty-eight (3.4%) of 1396 women seroconverted during pregnancy or <12 mo after delivery. This group of HIV-exposed children was at 2.3 times higher risk of infection (MTCT 20.5% [8 of 39] vs 9.0% (83 of 925]). An estimated 20% with CD4+ cell counts <350 would have been eligible for antiretroviral therapy (ART), yet all women with incident HIV infections are more likely to transmit HIV to their children. To ensure optimal prevention of MTCT, all women who seroconvert during pregnancy or lactation should be considered for ART for the purpose of prevention of MTCT, and women with CD4+ <350 should continue to receive ART.

Operational effectiveness of single-dose nevirapine in preventing mother-to-child transmission of HIV

OBJECTIVE To determine the operational effectiveness of the South African programme for preventing mother-to-child transmission (PMTCT) of HIV in reducing rates of early transmission of infection. METHODS Participants were mother-infant pairs who participated in the South African PMTCT programme between October 2002 and November 2004. This was a prospective cohort study. Three sites in different provinces were selected to represent differences in socioeconomic status and HIV prevalence. Data on antenatal care and labour ward care were obtained from maternal interviews and from reviews of medical records. A total of 665 mother-infant pairs in which the mother was HIV-positive were recruited and 588 (88.4%) were followed up at 3 or 4 weeks postpartum to determine the HIV status and vital status of the infant. FINDINGS Rural participants were significantly poorer and their health care was significantly worse. Women of higher socioeconomic status and those who received better counselling were more likely to be treated with nevirapine. Rates of early HIV transmission ranged from 8.6% to 13.7%. Maternal viral load was the only statistically significant risk factor for transmission. After adjusting for maternal viral load and prevalence of low birth weight, the odds of transmission were 1.8 times higher at the rural site. Controlling for having had > or = 4 antenatal visits and any delivery complication reduced the odds of transmission to 1.5 higher at the rural site. CONCLUSION Rates of early transmission of HIV in an operational setting using single-dose nevirapine administered both to mother and child are similar to those obtained in clinical trials. Scaling up access to antiretroviral regimens for women will further reduce transmission to infants.

Reliability of HIV rapid tests is user dependent : scientific letter

To the Editor: Rapid tests have been developed predominantly for the purposes of quick, easy-to-use, reliable on-site antibody testing for HIV by non-laboratory trained health professionals.1 The introduction of rapid tests to resource-limited countries has resolved many logistical issues including limited access to laboratories, delayed results turnaround time, limited laboratory expertise, and exorbitant costs of enzyme-linked immunosorbent assay (ELISA) technology.2,3OBJECTIVES Four widely used HIV rapid tests were evaluated in KwaZulu Natal to determine potential disparities in performance characteristics of rapid tests when used by nurses and counsellors as compared to skilled laboratory staff. DESIGN Whole blood samples from 961 pregnant women at 12 clinics that routinely provide Prevention of Mother-to-Child Transmission (PMTCT) services were tested on-site with 4 commercially available HIV rapid tests. Remaining whole blood specimens were tested with ELISA (Virology Laboratory) and 20% (191) of these were also tested with the four rapid tests by qualified laboratory staff. RESULTS The sensitivity and specificity of the rapid tests when performed by nurses and compared against the ELISA (Gold Standard) ranged from 92.5%-97.3% and 97.6%-98.2% respectively. Results of all four rapid tests performed by laboratory technicians on 211 samples were concordant with the ELISA results (sensitivity of 100%; 95%CI 95.9-100) and (specificity of 100%; 95%CI 96.5-100). CONCLUSIONS All four locally available HIV rapid tests meet international requirements however our data showcase the differences in performance characteristics when used by nursing and counselling staff at clinical sites as compared to skilled laboratory staff. Using such tests in a country of high HIV seroprevalence (30%), with an estimated 500 000 pregnant women testing for HIV annually, an estimated 3 600 (2.4%) and 7 000 (2%) women could be falsely diagnosed as HIV positive and negative respectively. These evaluations highlight the need for ongoing training, supervision and quality control to ensure reliable rapid HIV testing to avoid imminent litigations. Word count: 247

Rates of virological suppression and drug resistance in adult HIV-1-positive patients attending primary healthcare facilities in KwaZulu-Natal, South Africa

Background KwaZulu-Natal (KZN) Province in South Africa has the highest HIV disease burden in the country, with an estimated population prevalence of 24.7%. A pilot sentinel surveillance project was undertaken in KZN to classify the proportion of adult patients failing first-line ART and to describe the patterns of drug resistance mutations (DRMs) in patients with virological failure (VF). Methods Cross-sectional surveillance of acquired HIV drug resistance was conducted in 15 sentinel ART clinics between August and November 2013. Two population groups were surveyed: on ART for 12-15 months (Cohort A) or 24-36 months (Cohort B). Plasma specimens with viral load ≥1000 copies/mL were defined as VF and genotyped for DRMs. Results A total of 1299 adults were included in the analysis. The prevalence of VF was 4.0% (95% CI 1.8-8.8) among 540 adults in Cohort A and 7.7% (95% CI 4.4-13.0) of 759 adults in Cohort B. Treatment with efavirenz was more likely to suppress viral load in Cohort A (P = 0.005). Independent predictors of VF for Cohort B included male gender, advanced WHO stage at ART initiation and treatment with stavudine or zidovudine compared with tenofovir. DRMs were detected in 89% of 123 specimens with VF, including M184I/V, K103N/S, K65N/R, V106A/M and Y181C. Conclusions VF in adults in KZN was <8% up to 3 years post-ART initiation but was associated with a high frequency of DRMs. These data identify key groups for intensified adherence counselling and highlight the need to optimize first-line regimens to maintain viral suppression.

Polymorphisms in the Vitamin D receptor gene are associated with reduced rate of sputum culture conversion in multidrug-resistant tuberculosis patients in South Africa

Background Vitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established. We aimed to determine if SNPs in the VDR gene were associated with sputum culture conversion among a cohort of MDR TB patients in South Africa. Methods We conducted a prospective cohort study of adult MDR TB patients receiving second-line TB treatment in KwaZulu-Natal province. Subjects had monthly sputum cultures performed. In a subset of participants, whole blood samples were obtained for genomic analyses. Genomic DNA was extracted and genotyped with Affymetrix Axiom Pan-African Array. Cox proportional models were used to determine the association between VDR SNPs and rate of culture conversion. Results Genomic analyses were performed on 91 MDR TB subjects enrolled in the sub-study; 60% were female and median age was 35 years (interquartile range [IQR] 29–42). Smoking was reported by 21% of subjects and most subjects had HIV (80%), were smear negative (57%), and had cavitary disease (55%). Overall, 87 (96%) subjects initially converted cultures to negative, with median time to culture conversion of 57 days (IQR 17–114). Of 121 VDR SNPs examined, 10 were significantly associated (p<0.01) with rate of sputum conversion in multivariable analyses. Each additional risk allele on SNP rs74085240 delayed culture conversion significantly (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.67). Conclusions Polymorphisms in the VDR gene were associated with rate of sputum culture conversion in MDR TB patients in this high HIV prevalence setting in South Africa.

Spatial distribution of extensively drug-resistant tuberculosis (XDR TB) patients in KwaZulu-Natal, South Africa.

Background KwaZulu-Natal province, South Africa, has among the highest burden of XDR TB worldwide with the majority of cases occurring due to transmission. Poor access to health facilities can be a barrier to timely diagnosis and treatment of TB, which can contribute to ongoing transmission. We sought to determine the geographic distribution of XDR TB patients and proximity to health facilities in KwaZulu-Natal. Methods We recruited adults and children with XDR TB diagnosed in KwaZulu-Natal. We calculated distance and time from participants’ home to the closest hospital or clinic, as well as to the actual facility that diagnosed XDR TB, using tools within ArcGIS Network analyst. Speed of travel was assigned to road classes based on Department of Transport regulations. Results were compared to guidelines for the provision of social facilities in South Africa: 5km to a clinic and 30km to a hospital. Results During 2011–2014, 1027 new XDR TB cases were diagnosed throughout all 11 districts of KwaZulu-Natal, of whom 404 (39%) were enrolled and had geospatial data collected. Participants would have had to travel a mean distance of 2.9 km (CI 95%: 1.8–4.1) to the nearest clinic and 17.6 km (CI 95%: 11.4–23.8) to the nearest hospital. Actual distances that participants travelled to the health facility that diagnosed XDR TB ranged from <10 km (n = 143, 36%) to >50 km (n = 109, 27%), with a mean of 69 km. The majority (77%) of participants travelled farther than the recommended distance to a clinic (5 km) and 39% travelled farther than the recommended distance to a hospital (30 km). Nearly half (46%) of participants were diagnosed at a health facility in eThekwini district, of whom, 36% resided outside the Durban metropolitan area. Conclusions XDR TB cases are widely distributed throughout KwaZulu-Natal province with a denser focus in eThekwini district. Patients travelled long distances to the health facility where they were diagnosed with XDR TB, suggesting a potential role for migration or transportation in the XDR TB epidemic.

pncA Gene Mutations Associated with Pyrazinamide Resistance in Drug-Resistant Tuberculosis, South Africa and Georgia

Although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. We found polymorphisms in the pncA gene for 70% of multidrug-resistant and 96% of extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa and Georgia. Assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drug-resistant tuberculosis.

Improved Survival and Cure Rates With Concurrent Treatment for Multidrug-Resistant Tuberculosis–Human Immunodeficiency Virus Coinfection in South Africa

Background Mortality in multidrug-resistant (MDR) tuberculosis-human immunodeficiency virus (HIV) coinfection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR tuberculosis-HIV-coinfected patients on ART to those in patients with MDR tuberculosis alone. Methods This observational study enrolled culture-confirmed MDR tuberculosis patients with and without HIV in South Africa between 2011 and 2013. Participants received standardized MDR tuberculosis and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival. Results Among 206 participants, 150 were HIV infected, 131 (64%) were female, and the median age was 33 years (interquartile range [IQR], 26-41). Of the 191 participants with a final MDR tuberculosis outcome, 130 (73%) were cured or completed treatment, which did not differ by HIV status (P = .50). After 2 years, CD4 count increased a median of 140 cells/mm3 (P = .005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; P = .34). The strongest risk factor for mortality was having a CD4 count ≤100 cells/mm3 (adjusted hazards ratio, 15.6; 95% confidence interval, 4.4-55.6). Conclusions Survival and treatment outcomes among MDR tuberculosis-HIV individuals receiving concurrent ART approached those of HIV-uninfected patients. The greatest risk of death was among HIV-infected individuals with CD4 counts ≤100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR tuberculosis and HIV.

Congenital rubella syndrome surveillance in South Africa using a sentinel site approach: a cross-sectional study

Abstract Background Congenital rubella syndrome (CRS) includes disorders associated with intrauterine rubella infection. Incidence of CRS is higher in countries with no rubella-containing vaccines (RCV) in their immunization schedules. In the World Health Organization African region, RCVs are being introduced as part of the 2012–2020 global measles and rubella strategic plan. This study aimed to describe the epidemiology of confirmed CRS in South Africa prior to introduction of RCVs in the immunization schedule. Methods This was a descriptive study with 28 sentinel sites reporting laboratory-confirmed CRS cases in all 9 provinces of South Africa. In the retrospective phase (2010 to 2014), CRS cases were retrieved from medical records, and in the prospective phase (2015 to 2017) clinicians at study sites reported CRS cases monthly. Results There were 42 confirmed CRS cases in the retrospective phase and 53 confirmed CRS cases in the prospective phase. Most frequently reported birth defects were congenital heart disease and cataracts. The median age of mothers of CRS cases was 21 years in the retrospective phase (range: 11 to 38 years) and 22 years in the prospective phase (range: 15 to 38 years). Conclusion Baseline data on laboratory-confirmed CRS will enable planning and monitoring of RCV implementation in the South African Expanded Programme on Immunization program. Ninety-eight percent of mothers of infants with CRS were young women 14–30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV.