Strategic site selection for placement of HIV early infant diagnosis point-of-care technology within a national diagnostic network in Lesotho.

BACKGROUND: New technologies for rapid point-of-care (POC) diagnostic tests hold great potential for improving the health outcomes of HIV-exposed infants. POC testing for HIV early infant diagnosis (EID) was introduced in Lesotho in late 2016. Here we highlight critical requirements for selecting routine POC EID sites to ensure a sustainable and optimised EID diagnostic network. INTERVENTION: Lesotho introduced POC EID in a phased approach that included assessments of national databases to identify sites with high test volumes, the creation of local networks of sites to potentially increase access to POC EID, and a standardised capacity assessment to determine site readiness. Potential site networks comprising 'hub' testing sites and 'spoke' specimen referring sites were created. LESSONS LEARNT: After determining optimal placement, a total of 29 testing facilities were selected for placement of POC EID to potentially increase access to 189 facilities through the use of a hub-and-spoke model. Site capacity assessments identified vital human resources and infrastructure capacity gaps that needed to be addressed before introducing POC EID and informed appropriate POC platform selection. RECOMMENDATIONS: POC placement involves more than just purchasing the testing platforms. Considering the relatively small proportion of sites that can be eligible for placement of a POC platform, utilising a hub-and-spoke model can maximise the number of health facilities served by a POC platform while reducing the necessary capacity building and infrastructure investments to fewer sites.

24-Month HIV-free survival among HIV-exposed Infants in Lesotho: the PEAWIL cohort study.

INTRODUCTION: Following the implementation of the provision of lifelong antiretroviral therapy to all HIV-positive pregnant or breastfeeding women for prevention of mother-to-child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24-month HIV-free survival among HIV-exposed infants (HEIs). METHODS: We conducted a prospective observational cohort study that enrolled HIV-positive and HIV-negative pregnant women, with follow-up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow-up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV-free survival rates were computed using Kaplan-Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death. RESULTS: Between June 2014 and February 2016, we enrolled 653 HIV-positive and 941 HIV-negative pregnant women. Twenty-seven HIV-negative women acquired HIV during follow-up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV-unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24-month follow-up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow-up, 17 were found to be HIV-positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow-up were HIV-positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV-positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24-month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log-rank p = 0.065). HIV-free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants. CONCLUSIONS: The implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts.

Comparison of 6-week PMTCT outcomes for HIV-exposed and HIV-unexposed infants in the era of lifelong ART: Results from an observational prospective cohort study.

BACKGROUND: Lifelong antiretroviral therapy (ART) reduces mother-to-child HIV transmission (MTCT) and improves maternal health. Data on the outcomes of HIV-exposed infants (HEI) compared to their unexposed counterparts in the era of universal ART is limited. We compared birth and 6-week outcomes among infants born to HIV-positive and HIV-negative women in Lesotho. METHODS: 941 HIV-negative and 653 HIV-positive pregnant women were enrolled in an observational cohort to evaluate the effectiveness of prevention of mother-to-child HIV transmission (PMTCT) program after implementation of universal maternal ART in 14 health facilities. Pregnancy, delivery, birth, and 6-week data were collected through participant interviews and medical record review. DNA PCR testing for HEI was conducted within 2 weeks of birth and at around 6 weeks of age. Data were analysed to estimate the distribution of birth outcomes, mortality, HIV transmission and HIV-free survival at 6 weeks. RESULTS: HIV-positive women were older (mean age of 28.7 vs. 24.4 years) and presented for antenatal care earlier (mean gestational age of 23.0 weeks vs 25.3 weeks) than HIV-negative women. Prematurity was more frequent among HEI, 7.8% vs. 3.6%. There was no difference in rates of congenital anomalies between HEI (1.0%) and HIV-unexposed infants (HUI) (0.6%). Cumulative HIV transmission was 0.9% (N = 4/431) (95% CI:0.25-2.36) at birth and 1.0% (N = 6/583) (95% CI:0.38-2.23) at 6 weeks. Overall mortality, including stillbirths, was 5.2% and 6.0% by 6 weeks for HUI and HEI respectively. Among liveborn infants, 6-week HIV-free survival for HEI was 95.6% (95% CI:93.7-97.1) compared to 96.8% (95% CI:95.4-97.9) survival for HUI. CONCLUSIONS: Implementation of universal maternal ART lowers MTCT at 6 weeks of age with no differences in congenital anomalies or early mortality between HIV exposed Infants and HIV unexposed infants. However, HIV exposed infants continue to have high rates of prematurity despite improved maternal health on ART.

Community-Based Interventions to Reach 95-95-95 for Children and Adolescents: An Exploratory Programmatic Review From Lesotho.

BACKGROUND: Viral suppression is the desired outcome for children and adolescents with HIV. In this article, data from districts supporting community interventions (implementation districts) were reviewed and compared with data from districts without community interventions (nonimplementation districts) to explore a potential correlation between community interventions and clinical outcomes. SETTING: The study was based on data collected from facilities in 6 districts in Lesotho. METHODS: Twelve-month retention, viral load coverage, and viral suppression data from patients with ART between ages 5 and 24 from facilities in both district types were collected retrospectively. RESULTS: Implementation districts showed retention rates of 75%, with 5365 patients (47% of all patients on ART) having documented viral load results and 4641 (87%) being virally suppressed. Retention comparison demonstrated significantly higher rates in implementation districts (73%) as compared to (63%) in nonimplementation districts (P = 0.023). Viral load coverage and suppression comparison found that implementation district hospitals reported 632 (37% of total on ART) patients with a documented viral load, with 539 (85%) virally suppressed, whereas nonimplementation district hospitals reported 220 (31%) patients with viral load results, of whom 181 (82%) were suppressed. CONCLUSIONS: Overall, retention rates in the implementation districts were reasonable and were significantly better than the rates in the nonimplementation districts.

Conventional early infant diagnosis in Lesotho from specimen collection to results usage to manage patients: Where are the bottlenecks?

INTRODUCTION: Early infant diagnosis is an important step in identifying children infected with HIV during the perinatal period or in utero. Multiple factors contribute to delayed antiretroviral treatment initiation for HIV-infected children, including delays in the early infant HIV diagnosis cascade. METHODS: We conducted a retrospective study to evaluate early infant diagnosis turnaround times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8 weeks) who received an HIV test during 2011. Study sites were drawn from Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database data were linked to facility and laboratory register information. Turnaround time geometric means (with 95% CI) were calculated and compared by region using linear mixed models. RESULTS: 1,187 individual infant records from 25 facilities were reviewed. Overall, early infant diagnosis turnaround time was 61.7 days (95%CI: 55.3-68.7). Mean time from specimen collection to district laboratory was 14 days (95%CI: 12.1-16.1); from district to central laboratory, 2 days (95%CI 0.8-5.2); results from central laboratory to district hospital, 23.3 days (95%CI: 18.7-29.0); from district hospital to health facility, 3.2 days (95%CI 1.9-5.5); and from health facility to caregiver, 10.4 days (95%CI, 7.9-13.5). Mean times from specimen transfer to the central laboratory and for result transfer from central laboratory to district hospital were significantly shorter in the Lowlands Region (0.9 and 16.2 days, respectively), compared to Highlands Region (6.0 [P = 0.030] and 34.3 days [P = 0.0099]. Turnaround time from blood draw to receipt of results was significantly shorter for HIV infected infants compared to HIV uninfected infants [p = 0.0036] at an average of 47.1 days (95%CI: 38.9-56.9) and 62 days (95%CI: 55.9-68.7) respectively. Of 47 HIV-infected infants, 36 were initiated on antiretroviral therapy at an average of 1.3 days (95%CI: 0.3, 5.7) after caregiver received the result. CONCLUSION: HIV-infected infants received results earlier and were rapidly initiated on antiretroviral therapy once the result was delivered to caregiver. However, average early infant diagnosis turnaround time was two months; the longest period of delay was transfer of results from central laboratory to district hospital. Turnaround time of results based on geographical regions or between hospitals and health centres varied but did not reach statistical significance.

Pregnant and Postpartum Women's Experiences and Perspectives on the Acceptability and Feasibility of Copackaged Medicine for Antenatal Care and PMTCT in Lesotho.

Objective. To improve PMTCT and antenatal care-related service delivery, a pack with centrally prepackaged medicine was rolled out to all pregnant women in Lesotho in 2011. This study assessed acceptability and feasibility of this copackaging mechanism for drug delivery among pregnant and postpartum women. Methods. Acceptability and feasibility were assessed in a mixed method, cross-sectional study through structured interviews (SI) and semistructured interviews (SSI) conducted in 2012 and 2013. Results. 290 HIV-negative women and 437 HIV-positive women (n = 727) participated. Nearly all SI participants found prepackaged medicines acceptable, though modifications such as size reduction of the pack were suggested. Positive experiences included that the pack helped women take pills as instructed and contents promoted healthy pregnancies. Negative experiences included inadvertent pregnancy disclosure and discomfort carrying the pack in communities. Implementation was also feasible; 85.2% of SI participants reported adequate counseling time, though 37.8% felt pack use caused clinic delays. SSI participants reported improvement in service quality following pack introduction, due to more comprehensive counseling. Conclusions. A prepackaged drug delivery mechanism for ANC/PMTCT medicines was acceptable and feasible. Findings support continued use of this approach in Lesotho with improved design modifications to reflect the current PMTCT program of lifelong treatment for all HIV-positive pregnant women.

The association between HIV status and antenatal care attendance among pregnant women in rural hospitals in Lesotho.

OBJECTIVE: Early and frequent antenatal clinic (ANC) attendance is important for promotion of healthy outcomes for mother and child. This study explored the relationship between HIV status at the first ANC visit and subsequent ANC attendance among pregnant women in Lesotho. METHODS: A retrospective review of ANC records from a cohort of pregnant women attending their first ANC visit in December 2009 to May 2010 in 3 rural hospitals was conducted. Wilcoxon rank sum tests compared the distribution of gestational age (GA) and ANC visit number by HIV status. RESULTS: Records from 728 women were reviewed with mean GA at the first ANC visit of 22.3 weeks (SD = 7.2) and 2.7 (SD = 1.4) mean number of ANC visits per woman. Neither number of visits nor GA at first visit differed between HIV-positive and HIV-negative women. In total, 33.9% of women completed 4 ANC visits. Women with documented HIV-positive status before ANC were more likely to present early to ANC than all other women (18.8 vs. 22.6 weeks, adjusted odds ratio = 2.54, 95% confidence interval: 1.41 to 4.57). Geographical region, increasing maternal age, and lower parity were associated with completion of expected ANC visits among all women. Increasing maternal age and CD4 count were associated with completion of expected visits among HIV-positive women. CONCLUSIONS: In Lesotho, number of subsequent visits did not differ between women testing HIV-positive and HIV-negative in ANC. However, women with documented HIV-positive status attended ANC earlier than women who were tested in ANC. HIV testing and counseling, particularly for HIV-positive women before pregnancy, can promote early ANC attendance.

Preventing tuberculosis among HIV-infected pregnant women in Lesotho: the case for rolling out active case finding and isoniazid preventive therapy.

BACKGROUND: The Lesotho Ministry of Health issued guidelines on active case finding (ACF) for tuberculosis (TB) and isoniazid preventive therapy (IPT) in April 2011. ACF has been recommended in maternal and child health (MCH) settings globally, however, the feasibility of implementing IPT within MCH in countries with high concurrent HIV and TB epidemics is unknown. DESIGN/METHODS: The study evaluated the implementation of ACF and IPT guidelines in MCH settings in 2 health facilities in Lesotho. This descriptive prospective study analyzed data collected during routine services. Categorical data and continuous variables were summarized using descriptive statistics. The χ test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. RESULTS: Data from 160 HIV-positive and 640 HIV-negative women were reviewed. Within this study population, 99.8% of women were screened for TB, and 11.4% HIV-positive women compared with 2.3% HIV-negative women were reported to have symptoms of TB (P < 0.001). IPT was initiated in 124/158 (78.5%) HIV-positive pregnant women, 64.5% women completed a 6-month IPT regimen, 2 (1.6%) died of causes unrelated to IPT/TB, and 31.5% were lost to follow-up. Predictors of IPT initiation among HIV-positive women included gestational age at the first antenatal visit (unadjusted odds ratio, -0.93; 95% confidence interval: -0.88 to 0.98), and receipt of antiretroviral therapy for treatment rather than for prevention of mother-to-child transmission prophylaxis only (odds ratio, 4.59; 95% confidence interval: 1.32 to 15.93). CONCLUSIONS: Implementation of ACF and IPT is feasible within the MCH setting. Uptake of IPT during pregnancy among HIV-positive women was high, but with a high rate of loss to follow-up.

Adverse Events in HIV-Infected Persons Receiving Antiretroviral Drug Regimens in a Large Urban Slum in Nairobi, Kenya, 2003-2005.

OBJECTIVE: This article describes toxicities to antiretroviral therapy (ART) among HIV-infected patients receiving care at a clinic in a large urban slum in Nairobi, Kenya. METHODS: Patients were treated with nonnucleoside reverse transcriptase inhibitor-based ART and followed at scheduled intervals. Frequencies and cumulative probabilities of toxicities were calculated. RESULTS: Among 283 patients starting ART, any and severe clinical toxicity were recorded as 65% and 6%, respectively. Cumulative probabilities for remaining free of any and severe clinical toxicities at 6, 12, and 18 months, were 0.47, 0.26, and 0.17, respectively and 0.98, 0.95, and 0.89, respectively. The probability of remaining free from elevated and grade 3 or 4 serum aminotransferase (AST) at 6, 12, and 18 months were 0.62, 0.42, and 0.21, respectively, and 0.99 at 6, 12, and 18 months. CONCLUSIONS: ART toxicities were frequent, but severe toxicities were less common. In resource-limited settings, ART toxicity should not represent a barrier to care.

A program to provide antiretroviral therapy to residents of an urban slum in Nairobi, Kenya.

OBJECTIVE: To evaluate retention in care and response to therapy for patients enrolled in an antiretroviral treatment program in a severely resource-constrained setting. METHODS: We evaluated patients enrolled between February 26, 2003, and February 28, 2005, in a community clinic in Kibera, an informal settlement, in Nairobi, Kenya. Midlevel providers offered simplified, standardized antiretroviral therapy (ART) regimens and monitored patients clinically and with basic laboratory tests. Clinical, immunologic, and virologic indicators were used to assess response to ART; adherence was determined by 3-day recall. A total of 283 patients (70% women; median baseline CD4 count, 157 cells/ mm(3); viral load, 5.16 log copies/mL) initiated ART and were followed for a median of 7.1 months (n = 2384 patient-months). RESULTS: At 1 year, the median CD4 count change was +124.5 cells/mm(3) (n = 74; interquartile range, 42 to 180), and 71 (74%) of 96 patients had viral load <400 copies/mL. The proportion of patients reporting 100% adherence over the 3 days before monthly clinic visits was 94% to 100%. As of February 28, 2005, a total of 239 patients (84%) remained in care, 22 (8%) were lost to follow-up, 12 (4%) were known to have died, 5 (2%) had stopped ART, 3 (1%) moved from the area, and 2 (< 1% ) transferred care. CONCLUSIONS: Response to ART in this slum population was comparable to that seen in industrialized settings. With government commitment, donor support, and community involvement, it is feasible to implement successful ART programs in extremely challenging social and environmental conditions.