Oral HIV pre-exposure prophylaxis use among pregnant and postpartum women: results from real-world implementation in Lesotho.

Introduction: Lesotho has reached epidemic control, PrEP is an important component in maintaining that and in reaching the goal of eliminating mother-to-child transmission. Methods: We conducted a retrospective review of existing, routine PrEP health records in 26 health facilities in Lesotho. PrEP visit data were collected for pregnant and postpartum women screened for PrEP and/or enrolled in PrEP programs from 1 January 2019 through 30 June 2021 with follow-up data collected up to the date of data abstraction per site between October 2021 and May 2022. Poisson regression with robust variance was used to evaluate the association between patient characteristics and continuation of PrEP. Results: Indications for starting PrEP were significantly associated with continuation in PrEP use. Women starting PrEP due to having a partner known to be living with HIV were the most likely to return for follow-up. In all age groups, the most common reason for starting PrEP was being in a serodiscordant relationship, though the proportion varies by age. Conclusion: As Lesotho is now in the process of optimizing PrEP use among pregnant and postpartum women, it is critical to revise data sources to capture information that will link PrEP records and ANC/PNC records and document pregnancy/postpartum status in order to better understand PrEP use and gaps in this population.

Optimizing antiretroviral therapy for children living with HIV: Experience from an observational cohort in Lesotho.

INTRODUCTION: We describe transition of HIV-positive children from efavirenz- or nevirapine-based antiretroviral therapy (ART) to optimal dolutegravir (DTG) or lopinavir/ritonavir (LPV/r) (solid formulation)-based ART in Lesotho. METHODS: We followed a cohort of children less than 15 years of age who were initiated on ART on or after January 1, 2018 from 21 selected health facilities in Lesotho. From March 2020 to May 2022, we collected data retrospectively through chart abstraction and prospectively through caregiver interviews to cover a period of 24 months following treatment initiation. We used a structured questionnaire to collect data on demographics, ART regimen, drug formulations and switches, viral suppression, retention, and drug administration challenges. Data were summarized as frequencies and percentages, using SAS ver.9.4. RESULTS: Of 310 children enrolled in the study, 169 (54.5%) were female, and median age at ART initiation was 5.9 years (IQR 1.1-11.1). During follow-up, 19 (6.1%) children died, 41 (13.2%) were lost to follow-up and 74 (23.9%) transferred to non-study sites. At baseline, 144 (46.4%) children were receiving efavirenz-based ART regimen, 133 (42.9%) LPV/r, 27 (8.7%) DTG, 5 (1.6%) nevirapine; 1 child had incomplete records. By study end, 143 (46.1%) children were receiving LPV/r-based ART regimen, 109 (35.2%) DTG, and 58 (18.7%) were on efavirenz or nevirapine-based regimen. Of 116 children with viral load results after six months or more on a consistent regimen, viral suppression was seen in 35/53 (66.0%) children on LPV/r, 36/38 (94.7%) children on DTG and 19/24 (79.2%) children on efavirenz. CONCLUSION: Following optimal ART introduction in Lesotho, most children in the cohort were transitioned and many attained or maintained viral suppression after transition; however, we recommend more robust viral load monitoring and patient tracking to reduce losses and improve outcomes after ART transition.

Adverse Pregnancy Outcomes Among HIV-positive Women in the Era of Universal Antiretroviral Therapy Remain Elevated Compared With HIV-negative Women.

BACKGROUND: Without treatment, HIV infection in pregnant women is associated with adverse pregnancy outcomes. We compared adverse pregnancy outcomes among HIV-positive women on antiretroviral therapy (ART) and HIV-negative women who enrolled for antenatal care in selected health facilities in Maseru district, Lesotho. METHODS: We enrolled a cohort of HIV-positive and HIV-negative women at their first antenatal visit and followed them through delivery. Study data on miscarriage, stillbirth, preterm birth, low birth weight and birth defects were collected through participant interviews and medical record abstraction. We used the Rao-Scott χ2 test and the t test to assess differences in characteristics and outcomes between HIV-positive and HIV-negative women and generalized estimating equations for multivariable analysis. RESULTS: A total of 614 HIV-positive and 390 HIV-negative pregnant women were enrolled in the study with delivery information on 571 (93.1%) and 352 (90.3%) respectively. In the delivery cohort, the median age at enrolment was 28 years for HIV-positive women and 23 years for HIV-negative women with median gestational ages of 20 and 21 weeks, respectively. A total of 149 singleton pregnancies had documented adverse pregnancy outcomes; 33 (9.6%) HIV-negative pregnancies and 116 (20.6%) HIV-positive pregnancies. Compared with their HIV-negative counterparts, HIV-positive women were more likely to experience an adverse pregnancy outcome, adjusted odds ratio (AOR) 2.6 [95% confidence interval (CI): 1.71-3.97]; an intrauterine death (miscarriage or stillbirth), AOR 2.64 [95% CI: 1.25-5.49]; or a low birth weight delivery, AOR 1.89 [95% CI: 1.16-3.09]. CONCLUSION: Adverse pregnancy outcomes remained 2-3 times higher among HIV-positive women compared with HIV-negative women despite universal ART.

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.

Twelve-Month Outcomes of Community-Based Differentiated Models of Multimonth Dispensing of ART Among Stable HIV-Infected Adults in Lesotho: A Cluster-Randomized Noninferiority Trial.

BACKGROUND: Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facility-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho. METHODS: Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370). RESULTS: A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (-3.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = -0.1% [95% confidence interval (CI): -1.6% to 1.5%], adjusted RD = -1.3% (95% CI: -3.0% to 0.5%), and adjusted RD = -1.2% (95% CI: -2.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively. CONCLUSIONS: There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-of-care model.

Assessing Very Early Infant Diagnosis Turnaround Times: Findings from a Birth Testing Pilot in Lesotho.

Very early infant diagnosis (VEID) (testing within two weeks of life), combined with rapid treatment initiation, could reduce early infant mortality. Our study evaluated turnaround time (TAT) to receipt of infants' HIV test results and ART initiation if HIV-infected, with and without birth testing availability. Data from facility records and national databases were collected for 12 facilities offering VEID, as part of an observational prospective cohort study, and 10 noncohort facilities. HIV-exposed infants born in January-June 2016 and any cohort infant diagnosed as HIV-infected at birth or six weeks were included. The median TAT from blood draw to caregiver result receipt was 76.5 days at birth and 63 and 70 days at six weeks at cohort and noncohort facilities, respectively. HIV-exposed infants tested at birth were approximately one month younger when their caregivers received results versus those tested at six weeks. Infants diagnosed at birth initiated ART about two months earlier (median 6.4 weeks old) than those identified at six weeks (median 14.8 weeks). However, the long TAT for testing at both birth and six weeks illustrates the prolonged process for specimen transport and result return that could compromise the effectiveness of adding VEID to existing overburdened EID systems.

Virologic, immunologic and clinical response of infants to antiretroviral therapy in Kampala, Uganda.

BACKGROUND: Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda. METHODS: A prospective cohort of HIV-infected infants receiving treatment at the Baylor-Uganda clinic was analyzed. Patients were diagnosed, enrolled and followed up at the clinic. HIV viral load, CD4 cell counts and clinical progress were assessed during follow-up. Descriptive statistical analysis and logistic regression modeling to determine predictors of treatment success were conducted. RESULTS: Of 91 HIV-infected infants enrolled into the cohort, 53 (58.2%) infants were female; 43 (47.3%) were 6 months of age or younger, and 50 (55.6%) had advanced HIV/AIDS disease (Clinical stage 3 or 4). Eighty four infants started ART and 78 (92.9%) completed 6 months of treatments. Fifty six (71.8%) infants attained virologic suppression by month-6 of ART, and at month-12 of ART, the cumulative probability of attaining viral suppression was 83.1%. None of the baseline infant factors (age, sex, WHO stage, CD4 cell percent, weight for age, or height for age z-score) predicted treatment success. There was an increase in CD4 cells from a baseline mean of 23% to 30% at month-6 of treatment (p<0.001) and by month-24 of ART, the mean CD4 percent was 36%. A total of 7 patients died while on ART and another 7 experienced adverse events that were related to treatment. CONCLUSION: Our results show that, even among very young patients from resource constrained settings, ART dramatically suppresses HIV replication, allows immune recovery and clinical improvement, and is safe. However, baseline characteristics do not predict recovery in this age group.

Safety and tolerability of antiretroviral therapy among HIV-infected children and adolescents in Uganda.

BACKGROUND: Antiretroviral therapy (ART) is known to cause a number of adverse effects. The objective of this study was to determine the frequency and outcome of ART-related adverse events among patients aged 6 weeks to 18 years. METHODS: We followed up a cohort of 378 HIV-infected children and adolescents who started ART at the Baylor-Uganda Clinic during the period July 2004 to July 2009. Patients were started on zidovudine or stavudine, plus lamivudine, and efavirenz or nevirapine. Adverse events were recorded as they occurred. Descriptive analyses and Kaplan-Meier survival analysis were carried out. RESULTS: Of 126 adverse events reported among 107 (28.3%) patients, dizziness (17.5%), diarrhea (13.5%), and nausea and vomiting (14.3%) were the most frequent. Anxiety/night mares, skin rashes, nail discoloration, and lipodystrophy each contributed between 5% and 10%; whereas anorexia, abdominal pain, hepatitis, and somnolence contributed 1%-5%. Amnesia, lactic acidosis, gynaecomastia, cardiomyopathy, and peripheral neuropathy were rare, each contributing less than 1% of the total events. The overall probability of remaining free of adverse events was 77.1% (95% confidence interval: 72.38 to 81.13) at month 6 of ART.Among infants and young children, neurologic events could not be determined. Laboratory abnormalities were present at baseline and during follow-up, and hemoglobin levels increased significantly during the first 6 months of ART. There was no association between adverse events and baseline patient characteristics. CONCLUSION: Close to one-third of children on ART experience adverse events. Most events occur within the first 3 months of ART and are not associated with baseline patient characteristics.

Prevalence and outcome of HIV-associated malignancies among children.

OBJECTIVE: To determine the prevalence, associated factors, and outcome of HIV-associated malignancies among children enrolling for care at the Baylor-Uganda pediatric HIV clinic in Mulago Hospital, Kampala, Uganda. STUDY DESIGN: This was a retrospective case series involving records review of all HIV-infected patients who received care at the Baylor-Uganda clinic in Kampala, Uganda between 1 January 2004 and 31 December 2008. METHODS: Medical charts of the clinic patients aged 6 weeks to 18 years were retrieved for data abstraction. Data, including patient's age, sex, diagnosis, type of malignancy, anatomic location of the malignancy, pathology report, baseline laboratory results, and outcome of treatment, were abstracted. Proportions of malignancies among different groups were determined. In addition, Kaplan-Meier survival analysis was conducted. Change in CD4 cell percentages from baseline was assessed with the Wilcoxon signed-rank test. RESULTS: A total of 109 children with malignancies presented to the clinic during the study period, making up 1.67% of the total children visiting the clinic. Only two types of malignancies, Kaposi's sarcoma (90.7%) and non-Hodgkin's lymphoma (9.3%), were found. Deaths during follow-up were seen in the first few weeks to months. Upon starting treatment, the CD4 cell percentage increased significantly from a baseline median of 6-14% at 6 months to 15.8% at 12 months of follow-up. CONCLUSION: HIV-associated malignancies remain an important cause of morbidity and mortality among HIV-infected children in Uganda. Many affected children die in the first weeks of treatment, but those who survive mount good immunologic recovery.