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

Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women.

BACKGROUND: We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. METHODS: The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. RESULTS: The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1-2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4 cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1-3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4 cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7-1.1) and those who initiated ART in pregnancy. CONCLUSION: The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART

Effects of Sex, Age, and Season on Plasma Steroids in Free-ranging Texas Horned Lizards (Phrynosoma cornutum)

The Texas horned lizard (Phrynosoma cornutum) is protected in several states due to its apparently declining numbers; information on its physiology is therefore of interest from both comparative endocrine and applied perspectives. We collected blood samples from free-ranging P. cornutum in Oklahoma from April to September 2005, spanning their complete active period. We determined plasma concentrations of the steroids, progesterone (P), testosterone (T), and corticosterone (CORT) by radioimmunoassay following chromatographic separation and 17β-estradiol (E2) by direct radioimmunoassay. T concentrations in breeding males were significantly higher than in non-breeding males. P showed no significant seasonal variation within either sex. CORT was significantly higher during the egg-laying season compared to breeding and non-breeding seasons for adult females and it was marginally higher in breeding than in non-breeding males (P = 0.055). CORT concentrations also significantly increased with handling in non-breeding males and egg-laying females. Perhaps most surprisingly, there were no significant sex differences in plasma concentrations of P and E2. Furthermore, with respect to seasonal differences, plasma E2 concentrations were significantly higher in breeding females than in egg-laying or non-breeding females, and they were significantly higher in breeding than in non-breeding males. During the non-breeding season, yearling males exhibited higher E2 concentrations than adult males; no other differences between the steroid concentrations of yearlings and adults were detected. In comparison to other vertebrates, the seasonal steroid profile of P. cornutum exhibited both expected and unexpected patterns, and our results illustrate the value of collecting such baseline data as a springboard for appropriate questions for future research

Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study among HIV-infected adults initiating HAART in South Africa

<p>Abstract</p> <p>Background</p> <p>As stavudine remains an important and widely prescribed drug in resource-limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question.</p> <p>Methods</p> <p>We analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six- and/or 12-month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression.</p> <p>Results</p> <p>Between 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13-2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86-5.25), lipoatrophy (OR 11.8; 95% CI 3.2-43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83-18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates.</p> <p>Conclusions</p> <p>Lower stavudine dosage is associated with fewer reports of several stavudine-associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART.</p

Deciphering top flavor violation at the LHC with B factories

The LHC will have unprecedented sensitivity to flavor-changing neutral current (FCNC) top quark decays, whose observation would be a clear sign of physics beyond the standard model. Although many details of top flavor violation are model dependent, the standard model gauge symmetries relate top FCNCs to other processes, which are strongly constrained by existing data. We study these constraints in a model independent way, using a low energy effective theory from which the new physics is integrated out. We consider the most important operators which contribute to top FCNCs and analyze the current constraints on them. We find that the data rule out top FCNCs at a level observable at the LHC due to most of the operators comprising left-handed first or second generation quark fields, while there remains a substantial window for top decays mediated by operators with right-handed charm or up quarks. If FCNC top decays are observed at the LHC, such an analysis may help decipher the underlying physics.Comment: 17 pages, 5 figures; some typos correcte

Cohort profile: the Right to Care Clinical HIV Cohort, South Africa

PURPOSE: The research objectives of the Right to Care Clinical HIV Cohort analyses are to: (1) monitor treatment outcomes (including death, loss to follow-up, viral suppression and CD4 count gain among others) for patients on antiretroviral therapy (ART); (2) evaluate the impact of changes in the national treatment guidelines around when to initiate ART on HIV treatment outcomes; (3) evaluate the impact of changes in the national treatment guidelines around what ART regimens to initiate on drug switches; (4) evaluate the cost and cost-effectiveness of HIV treatment delivery models; (5) evaluate the need for and outcomes on second-line and third-line ART; (6) evaluate the impact of comorbidity with non-communicable diseases on HIV treatment outcomes and (7) evaluate the impact of the switch to initiating all patients onto ART regardless of CD4 count. PARTICIPANTS: The Right to Care Clinical HIV Cohort is an open cohort of data from 10 clinics in two provinces within South Africa. All clinics include data from 2004 onwards. The cohort currently has data on over 115 000 patients initiated on HIV treatment and patients are followed up every 3–6 months for clinical and laboratory monitoring. FINDINGS TO DATE: Cohort data includes information on demographics, clinical visit, laboratory data, medication history and clinical diagnoses. The data have been used to identify rates and predictors of first-line failure, to identify predictors of mortality for patients on second-line (eg, low CD4 counts) and to show that adolescents and young adults are at increased risk of unsuppressed viral loads compared with adults. FUTURE PLANS: Future analyses will inform national models of HIV care and treatment to improve HIV care policy in South Africa

Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa

<p>Abstract</p> <p>Background</p> <p>Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV.</p> <p>Results</p> <p>We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm³) and CD4 (90 vs. 80 cells/mm³) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable.</p> <p>Conclusions</p> <p>We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.</p

The net cost of incorporating resistance testing into HIV/AIDS treatment in South Africa: a Markov model with primary data

<p>Abstract</p> <p>Background</p> <p>Current guidelines for providing antiretroviral therapy (ART) in South Africa's public sector programme call for switching patients from first-line to second-line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first-line therapy, rather than switching all failures to second-line therapy.</p> <p>Methods</p> <p>Costs were estimated for three scenarios: routine maintenance (standard care without resistance testing, switch all failures to second line); resistance testing (resistance test for patients with failure, switch those with resistance); and limited testing (resistance test for patients with failure in the first three years, switch those with resistance). A Markov model was used to estimate the cost of each arm over five years after first line initiation. Rates of treatment failure, viral resistance and treatment costs were estimated with primary data from a large HIV treatment cohort at a public facility in Johannesburg. Future costs were discounted at 3%.</p> <p>Results</p> <p>Virological failure rates over five years were 19.8% in routine maintenance and 20.2% in resistance testing and limited testing; 16.8% and 11.4% of failures in routine and limited testing, respectively, did not have any resistance mutations, resulting in 3.1% and 2.0% fewer patients switching to second-line ART by the end of five years. Treatment costs were estimated at US$526 and$1268 per patient per year on first-line and second-line therapy, respectively; a resistance test cost $242. The total average cost per patient over five years was$2780 in routine maintenance; $2775 in resistance testing; and$2763 in limited testing.</p> <p>Conclusions</p> <p>Incorporating resistance testing into treatment guidelines in South Africa is potentially cost-neutral and can identify other reasons for failure, conserve treatment options, and generate information about emerging resistance patterns.</p

Health facility and skilled birth deliveries among poor women with Jamkesmas health insurance in Indonesia: a mixed-methods study

BACKGROUND: The growing momentum for quality and affordable health care for all has given rise to the recent global universal health coverage (UHC) movement. As part of Indonesia’s strategy to achieve the goal of UHC, large investments have been made to increase health access for the poor, resulting in the implementation of various health insurance schemes targeted towards the poor and near-poor, including the Jamkesmas program. In the backdrop of Indonesia’s aspiration to reach UHC is the high rate of maternal mortality that disproportionally affects poor women. The objective of this study was to evaluate the association of health facility and skilled birth deliveries among poor women with and without Jamkesmas and explore perceived barriers to health insurance membership and maternal health service utilization. METHODS: We used a mixed-methods design. Utilizing data from the 2012 Indonesian Demographic and Health Survey (n = 45,607), secondary analysis using propensity score matching was performed on key outcomes of interest: health facility delivery (HFD) and skilled birth delivery (SBD). In-depth interviews (n = 51) were conducted in the provinces of Jakarta and Banten among poor women, midwives, and government representatives. Thematic framework analysis was performed on qualitative data to explore perceived barriers. RESULTS: In 2012, 63.0% of women did not have health insurance; 19.1% had Jamkesmas. Poor women with Jamkesmas were 19% (OR = 1.19 [1.03–1.37]) more likely to have HFD and 17% (OR = 1.17 [1.01–1.35]) more likely to have SBD compared to poor women without insurance. Qualitative interviews highlighted key issues, including: lack of proper documentation for health insurance registration; the preference of pregnant women to deliver in their parents’ village; the use of traditional birth attendants; distance to health facilities; shortage of qualified health providers; overcrowded health facilities; and lack of health facility accreditation. CONCLUSION: Poor women with Jamkesmas membership had a modest increase in HFD and SBD. These findings are consistent with economic theory that health insurance coverage can reduce financial barriers to care and increase service uptake. However, factors such as socio-cultural beliefs, accessibility, and quality of care are important elements that need to be addressed as part of the national UHC agenda to improve maternal health services in Indonesia