Mobility and Clinic Switching Among Postpartum Women Considered Lost to HIV Care in South Africa.

This version is the Accepted Manuscript, and was published in final edited form as: J Acquir Immune Defic Syndr. 2017 April 01; 74(4): 383–389. doi:10.1097/QAI.0000000000001284OBJECTIVE: Retention in HIV care, particularly among postpartum women, is a challenge to national antiretroviral therapy programs. Retention estimates may be underestimated because of unreported transfers. We explored mobility and clinic switching among patients considered lost to follow-up (LTFU). DESIGN: Observational cohort study. METHODS: Of 788 women initiating antiretroviral therapy during pregnancy at 6 public clinics in Johannesburg, South Africa, 300 (38.1%) were LTFU (no visit ≥3 months). We manually searched for these women in the South African National Health Laboratory Services database to assess continuity of HIV care. We used geographic information system tools to map mobility to new facilities. RESULTS: Over one-third (37.6%) of women showed evidence of continued HIV care after LTFU. Of these, 67.0% continued care in the same province as the origin clinic. Compared with those who traveled outside of the province for care, these same-province "clinic shoppers" stayed out-of-care longer {median 373 days [interquartile range (IQR): 175-790] vs. 175.5 days (IQR: 74-371)} and had a lower CD4 cell count on re-entry [median 327 cells/μL (IQR: 196-576) vs. 493 cells/μL (IQR: 213-557). When considering all women with additional evidence of care as engaged in care, cohort LTFU dropped from 38.1% to 25.0%. CONCLUSION: We found evidence of continued care after LTFU and identified local and national clinic mobility among postpartum women. Laboratory records do not show all clinic visits and manual matching may have been under- or overestimated. A national health database linked to a unique identifier is necessary to improve reporting and patient care among highly mobile populations

Early diagnosis of human immunodeficiency virus infection status in vertically exposed infants in a low resource setting.

Student Number : 8403267 - PhD thesis - School of Pathology - Faculty of Health SciencesSub-Saharan Africa is the eye of the HIV epidemic. This study was conducted when treatment for the majority of HIV-infected patients in low resource settings was considered unattainable and the risks of diagnosing HIV often outweighed the benefits. Coupled with the complexities of HIV diagnosis in infancy, children typically were only diagnosed once already ill or not at all. Key strategies to address the paediatric epidemic focused on preventing mother to child transmission and reducing mortality and morbidity of infected children predominantly with co-trimoxazole prophylaxis. Both strategies required early diagnosis of HIV infection in infancy for monitoring prevention programs and identifying infected children respectively. The diagnostic algorithm for resource limited settings recommended the use of inexpensive, technically simpler HIV antibody detection assays that are unsuitable for use in HIV-exposed children under 12-months of age. Paradoxically this algorithm provided a barrier to HIV diagnosis in children because of high loss to follow-up rates and death in the first year of life. The objective of this study was to establish an accurate, affordable diagnostic algorithm for early diagnosis of HIV infection that could be rapidly implemented in South Africa and benefit other resource limited settings. The HIV infection status of 300 vertically exposed infants was determined according to first world criteria in a prospective, cohort study at Coronation Hospital, Johannesburg over 21 months. This status was used to assess the accuracy of clinical examinations and HIV assays in diagnosing HIV at 6-weeks, 3-, 7- and 12-months of age. The average cost of determining an infant’s HIV infection status was measured. A single HIV DNA PCR test at 6-weeks of age proved highly accurate in determining HIV status at a marginally increased cost to government and was incorporated by the South African Department of Health into national policy. The ultrasensitive p24 antigen assay and HIV antibody detection assays on serum and oral fluid were identified as valuable candidates where PCR testing is unavailable. Dried blood spot samples from heelpricks are critical for policy to be translated into practice since skills to perform venesection in 6-week old babies are limited. The next challenge lies in operationalising these findings at a clinical and laboratory level to the benefit of the 300 000 South African children annually exposed to HIV at birth. The urgency of early diagnosis has been increased by the availability of highly effective antiretroviral therapy

Identifying HIV infection in South African women: How does a fourth generation HIV rapid test perform?

Background: HIV rapid tests (RT) play an important role in tackling the HIV pandemic in South Africa. Third generation RT that detect HIV antibodies are currently used to diagnose HIV infection at the point of care. Determine Combo (DC) is the first fourth generation RT that detects both p24 antigen (p24Ag) and HIV antibodies (Ab), theoretically reducing the window period and increasing detection rates. Early detection of maternal HIV infection is important to mitigate the high risk of vertical transmission associated with acute maternal infection. Objectives: We assessed the performance of the DC RT against third generation RT in antenatal and post-partum women. Methods: Third generation RT Advance Quality and Acon were used in a serial algorithm to diagnose HIV infection in antenatal and post-partum women over six months at a tertiary hospital in Johannesburg, South Africa. This data provided the reference against which the DC RT was compared on plasma and whole blood samples. Results: The 1019 participants comprised 345 (34%) antenatal and 674 (66%) post-partum women. Ninety women (8.8%) tested HIV-positive of whom 59 (66%) were tested antenatally, and 31 (34%) post-partum yielding prevalence rates of 17.1% and 4.6% respectively. The sensitivity and specificity of the Ab component of DC on plasma antenatally was 100% (93.8% – 100%) and 100% (98.6% – 100%) respectively and post-partum was 100% (88.9% – 100%) and 99.6% (98.8% – 99.9%) respectively. One false positive and not a single true positive p24Ag was detected. Of 505 post-partum women who tested HIV-negative 6–12 months prior to enrolment, 12 (2.4%) seroconverted. Conclusion: The fourth generation DC offered no advantage over current third generation RT in the diagnosis of HIV infection

Time to implement 9-month infant HIV testing in South Africa

Background. South Africa (SA) is likely to meet the National Strategic Plan target of <2% mother-to-child HIV transmission at 6 weeks of age in 2015. Children infected with HIV after 6 weeks often remain undiagnosed because of poor implementation of post-weaning and final outcome 18-month HIV testing. The World Health Organization recommends a screening HIV rapid test (HRT) in HIV-exposed infants at the 9-month immunisation visit to exclude postnatal infection, with a confirmatory HIV polymerase chain reaction (PCR) test if the HRT is positive.Objective. To evaluate the impact of substituting this recommendation for the post-weaning HIV testing recommended by SA guidelines.Methods. Rates of seroreversion and probability of infection at 9 months of age were applied to a theoretical population of 100 HIV-exposed infants, uninfected at birth and breastfed for 1 year with antiretroviral prophylaxis. Nine scenarios were developed and the number of HIV PCRs saved compared with current guidelines was calculated.Results. Nine-month testing using the HRT reduced the number of follow-up PCR tests done in all scenarios by >50%, with differences ranging from 51% to 59% and 81% to 89% for low and high seroreversion rates, respectively.Conclusions. Nine-month testing using HRT would increase identification and early treatment of HIV-infected infants, improve monitoring of postnatal transmission rates, and reduce the number of HIV PCR tests done with resultant cost saving. Training of healthcare workers implementing HRT would be required. Ongoing efforts to improve implementation and monitoring of testing at 9 and 18 months will be essential

Eliminating Vertical Transmission of HIV in South Africa: Establishing a Baseline for the Global Alliance to End AIDS in Children

To gain a detailed overview of vertical transmission in South Africa, we describe insights from the triangulation of data sources used to monitor the national HIV program. HIV PCR results from the National Health Laboratory Service (NHLS) were analysed from the National Institute of Communicable Diseases (NICD) data warehouse to describe HIV testing coverage and positivity among children <2 years old from 2017–2021. NICD data were compared and triangulated with the District Health Information System (DHIS) and the Thembisa 4.6 model. For 2021, Thembisa estimates a third of children living with HIV go undiagnosed, with NICD and DHIS data indicating low HIV testing coverage at 6 months (49%) and 18 months (33%) of age, respectively. As immunisation coverage is reported at 84% and 66% at these time points, better integration of HIV testing services within the Expanded Programme for Immunization is likely to yield improved case findings. Thembisa projects a gradual decrease in vertical transmission to 450 cases per 100,000 live births by 2030. Unless major advances and strengthening of maternal and child health services, including HIV prevention, diagnosis, and care, can be achieved, the goal to end AIDS in children by 2030 in South Africa is unlikely to be realised

KIR-HLA and Maternal-Infant HIV-1 Transmission in Sub-Saharan Africa

Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized. Although a number of significant associations were determined in both the total group and in the nevirapine (NVP) exposed group, the most significant findings involved KIR2DL2 and KIR2DL3 and HLA-C. KIR2DL2/KIR2DL3 was underrepresented in intrapartum (IP)-transmitting mothers compared to non-transmitting (NT) mothers (P = 0.008) and remained significant (P = 0.036) after correction for maternal viral load (MVL). Homozygosity for KIR2DL3 alone and in combination with HLA-C allotype heterozygosity (C1C2) was elevated in IP-transmitting mothers compared to NT mothers (P = 0.034 and P = 0.01 respectively), and after MVL correction (P = 0.033 and P = 0.027, respectively). In infants, KIR2DL3 in combination with its HLA-C1 ligand (C1) as well as homozygosity for KIR2DL3 with C1C2, were both found to be underrepresented in infected infants compared to exposed uninfected infants in the total group (P = 0.06 and P = 0.038, respectively) and in the sub-group of infants whose mothers received NVP (P = 0.007 and P = 0.03, respectively). These associations were stronger post MVL adjustment (total group: P = 0.02 and P = 0.009, respectively; NVP group: P = 0.004 and P = 0.02, respectively). Upon stratification according to low and high MVL, all significant associations fell within the low MVL group, suggesting that with low viral load, the effects of genotype can be more easily detected. In conclusion this study has identified a number of significant associations that suggest an important role for NK cells in maternal-to-infant HIV-1 transmission

KIR-HLA and Maternal-Infant HIV-1 Transmission in Sub-Saharan Africa

Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized. Although a number of significant associations were determined in both the total group and in the nevirapine (NVP) exposed group, the most significant findings involved KIR2DL2 and KIR2DL3 and HLA-C. KIR2DL2/KIR2DL3 was underrepresented in intrapartum (IP)-transmitting mothers compared to non-transmitting (NT) mothers (P = 0.008) and remained significant (P = 0.036) after correction for maternal viral load (MVL). Homozygosity for KIR2DL3 alone and in combination with HLA-C allotype heterozygosity (C1C2) was elevated in IP-transmitting mothers compared to NT mothers (P = 0.034 and P = 0.01 respectively), and after MVL correction (P = 0.033 and P = 0.027, respectively). In infants, KIR2DL3 in combination with its HLA-C1 ligand (C1) as well as homozygosity for KIR2DL3 with C1C2, were both found to be underrepresented in infected infants compared to exposed uninfected infants in the total group (P = 0.06 and P = 0.038, respectively) and in the sub-group of infants whose mothers received NVP (P = 0.007 and P = 0.03, respectively). These associations were stronger post MVL adjustment (total group: P = 0.02 and P = 0.009, respectively; NVP group: P = 0.004 and P = 0.02, respectively). Upon stratification according to low and high MVL, all significant associations fell within the low MVL group, suggesting that with low viral load, the effects of genotype can be more easily detected. In conclusion this study has identified a number of significant associations that suggest an important role for NK cells in maternal-to-infant HIV-1 transmission

A matter of context – time to clinically validate 9-month infant HIV testing in South Africa(?)

Mazanderani comments on an article by Fairlie at al. (September 2015 SAMJ)