Association of Maternal Viral Load and CD4 Count With Perinatal HIV-1 Transmission Risk During Breastfeeding in the PROMISE Postpartum Component.

BACKGROUND: Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the Promoting Maternal-Infant Survival Everywhere trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (<1%) in the 2 arms. We assessed whether maternal viral load (MVL) and CD4 cell counts were associated with breastfeeding HIV transmission. METHODS: MVL was collected at entry (7-14 days postpartum) and at weeks 6, 14, 26, and 50 postpartum. CD4 cell counts were collected at entry and weeks 14, 26, 38, and 50 postpartum. Infant HIV-1 nucleic acid test was performed at weeks 1 and 6, every 4 weeks until week 26, and then every 12 weeks. The associations of baseline and time-varying MVL and CD4 cell counts with transmission risk were assessed using time-to-event analyses by randomized treatment arm. RESULTS: Two thousand four hundred thirty-one mother-infant pairs were enrolled in the study. Baseline MVL (P = 0.11) and CD4 cell counts (P = 0.51) were not significantly associated with infant HIV-1 infection. Time-varying MVL was significantly associated with infant HIV-1 infection {hazard ratio [95% confidence interval (CI)]: 13.96 (3.12 to 62.45)} in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 1.04 (0.20 to 5.39)]. Time-varying CD4 cell counts were also significantly associated with infant HIV-1 infection [hazard ratio (95% CI): 0.18 (0.03 to 0.93)] in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 0.38 (0.08 to 1.77)]. CONCLUSIONS: In women receiving mART, increased MVL and decreased CD4 cell counts during breastfeeding were associated with increased risk of infant HIV-1 infection.

The impact of short term Antiretroviral Therapy (ART) interruptions on longer term maternal health outcomes-A randomized clinical trial.

BACKGROUND: Given well documented challenges faced by pregnant women living with HIV taking lifetime ART, it is critical to understand the impact of short-term ART exposure followed by treatment interruption on maternal health outcomes. METHODS: HIV+ breastfeeding (BF) and Formula Feeding (FF) women with CD4 counts > 350 cells/mm3, enrolled in the 1077BF/1077FF PROMISE trial were followed to assess the effect of ART during pregnancy and breastfeeding respectively. The first analysis compared ART use limited to the antepartum period (AP-only) relative to women randomized to Zidovudine. The second analysis included women with no pregnancy combination ART exposure; and compared women randomized to either ART or no ART during postpartum (PP-only). Both analyses included follow-up time beyond breastfeeding period. The primary outcome was progression to AIDS and/or death. Secondary outcomes included adverse events and HIV-related events. RESULTS: 3490 and 1137 HIV+ women were enrolled from 14 sites in Africa and India from April 2011 through September 2014 in cohort AP-only and PP-only, respectively. Most were Black African (96%); median age was 27 years; 97% were WHO Clinical Stage I; and most had a screening CD4 count ≥500 cells/mm3 (78%). The rate of progression to AIDS and/or death was similar and low across all comparison arms (AP comparison, HR = 1.14, 95%CI (0.44, 2.96), p-value = 0.79). In the PP-only cohort, the rate of WHO stage 2-3 events was lower for women randomized to ART(HR = 0.65, 95% CI 0.42, 1.01, p-value = 0.05). CONCLUSION: The incidence of AIDS and/or death was low in pregnant/postpartum HIV+ women with highCD4 cell counts for all comparison arms. This provides some reassurance that there were limited consequences for short term ART interruption in this group of asymptomatic HIV+ women during up to 4 years of follow up; and underscores that even short term ART exposure postpartum may reduce the risk of WHO grade 2-3 disease progression.

Characteristics and outcomes of traumatic spinal cord injury in a low-resource setting.

Spinal cord injury (SCI) is relatively rare and affects an estimated 15-40 per 1 million people globally. All patients admitted from October 2016 to June 2017 at Kamuzu Central Hospital, Malawi with a spinal column injury were retrospectively studied. Out of 1442 patients, 46 had vertebral column injury, and half of these had neurological deficit. The most common mechanism of injury was road traffic crash (45.7%), and cervical SCIs were the most common (41.3%). The overall mortality was 15.2%, thus demonstrating devastating morbidity and mortality. Owing to the latter, and the relative lack of operative facilities, primary prevention remains the most effective way to attenuate the tragedy of SCIs.

Etiology of major limb amputations at a tertiary care centre in Malawi.

Introduction: Amputations in low- and middle-income countries (LMICs) represent an important cause of disability and economic hardship. LMIC patients are young and suffer from preventable causes, such as trauma and trauma-related infections. We herein studied the etiology in amputations in a Malawian tertiary care hospital over a 9-year period. Methods: Operative and anaesthesia logs at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, were reviewed for 2008-2016. Baseline demographic and clinical variables and type of amputation performed were collected. Only major limb amputations, defined as above or below the knee, above or below the elbow, and above the wrist, were included in this study. Results: A total of 610 patients underwent 630 major amputations during the study period. Of these, 170 (27%) patients were female, and the median age of the cohort was 39 (interquartile range [IQR] 25-55). Of these patients, 345 (54.8%) had infection or gangrene recorded among the indications for amputation, 203 (32.2%) had trauma, 94 (14.9%) had cancer and 67 (10.6%) had documented diabetes. Women underwent diabetes-related amputations more often than men (37 out of 67, or 56.1%), and were significantly younger when their amputations were due to diabetes (median age 48 vs 53 years old, P=0.004) or trauma (median age 21 vs 30 years old, P=0.02). The commonest operative procedures were below the knee amputations, at 271 (43%), and above the knee amputations, at 213 (33.8%). Conclusion: Amputations in Malawi affect primarily the young, in the most economically productive time of their lives, in contrast to amputees in high-income countries. Preventable causes, such as infection and trauma, lead to the majority of amputations. These etiologies represent an important primary prevention target for public health efforts in LMICs.

Prevention of HIV-1 Transmission Through Breastfeeding: Efficacy and Safety of Maternal Antiretroviral Therapy Versus Infant Nevirapine Prophylaxis for Duration of Breastfeeding in HIV-1-Infected Women With High CD4 Cell Count (IMPAACT PROMISE): A Randomized, Open-Label, Clinical Trial.

BACKGROUND: No randomized trial has directly compared the efficacy of prolonged infant antiretroviral prophylaxis versus maternal antiretroviral therapy (mART) for prevention of mother-to-child transmission throughout the breastfeeding period. SETTING: Fourteen sites in Sub-Saharan Africa and India. METHODS: A randomized, open-label strategy trial was conducted in HIV-1-infected women with CD4 counts ≥350 cells/mm (or ≥country-specific ART threshold if higher) and their breastfeeding HIV-1-uninfected newborns. Randomization at 6-14 days postpartum was to mART or infant nevirapine (iNVP) prophylaxis continued until 18 months after delivery or breastfeeding cessation, infant HIV-1 infection, or toxicity, whichever occurred first. The primary efficacy outcome was confirmed infant HIV-1 infection. Efficacy analyses included all randomized mother-infant pairs except those with infant HIV-1 infection at entry. RESULTS: Between June 2011 and October 2014, 2431 mother-infant pairs were enrolled; 97% of women were World Health Organization Clinical Stage I, median screening CD4 count 686 cells/mm. Median infant gestational age/birth weight was 39 weeks/2.9 kilograms. Seven of 1219 (0.57%) and 7 of 1211 (0.58%) analyzed infants in the mART and iNVP arms, respectively, were HIV-infected (hazard ratio 1.0, 96% repeated confidence interval 0.3-3.1); infant HIV-free survival was high (97.1%, mART and 97.7%, iNVP, at 24 months). There were no significant differences between arms in median time to breastfeeding cessation (16 months) or incidence of severe, life-threatening, or fatal adverse events for mothers or infants (14 and 42 per 100 person-years, respectively). CONCLUSIONS: Both mART and iNVP prophylaxis strategies were safe and associated with very low breastfeeding HIV-1 transmission and high infant HIV-1-free survival at 24 months.

Reproductive intentions and family planning practices of pregnant HIV-infected Malawian women on antiretroviral therapy.

The objective of this study was to describe the pregnancy intentions of pregnant HIV-infected Malawian women on antiretroviral therapy (ART) for at least 6 months prior to the current pregnancy, and to assess whether time on ART was associated with pregnancy intention. We conducted a cross-sectional analysis of HIV-infected Malawian women receiving antenatal care at a government hospital with a survey assessing ART history, reproductive history, and family planning use at conception. We used Pearson's chi-square tests and Fisher's exact tests to compare these parameters between women on ART greater than 24 months with those on ART less than 24 months. Modified Poisson regression was performed to assess the association between time on ART and pregnancy intention. Most women (75%) reported that their current pregnancy was unintended, defined as either Mistimed (21%) or Unwanted (79%). Women on ART for longer than 2 years were more likely to report an unintended pregnancy (79% versus 65%, p = .03), though there was no significant association between time on ART and pregnancy intention in multivariate analysis. Most women (79%) were using contraception at the time of conception, with condoms being most popular (91%), followed by injectables (9%) and the implant (9%). HIV-infected women on ART continue to experience high rates of unintended pregnancy in the Option B+ era. As Option B+ continues to be implemented in Malawi and increasing numbers of HIV-infected women initiate lifelong ART, ensuring that the most effective forms of contraception are accessible is necessary to decrease unintended pregnancy.

Prevalence of drug resistant TB among outpatients at an HIV/TB clinic in Lilongwe, Malawi.

BACKGROUND: We sought to determine the prevalence of drug resistant TB among outpatients initiating TB treatment in Lilongwe, Malawi. METHODS: This was a prospective cohort study of patients 18 years and older initiating TB treatment at Martin Preuss Centre, the primary integrated HIV/TB clinic in Lilongwe, Malawi, from April 2011 to July 2012. Procedures included questionnaires, physical exam, chest x-ray, full blood count and sputum collection. Sputum samples underwent acid-fast bacilli (AFB) smear testing and culture by Lowenstein-Jensen (LJ) and liquid Mycobacteria Growth Indicator Tube (MGIT) methods. Drug sensitivity was investigated using the Hain GenoType MTBDRplus line probe assay. RESULTS: Of the 702 patients, 219 (31.2%) were female and 653 (93.0%) were presenting for first-time TB treatment. HIV co-infection was present in 420 (59.8%) cases, with 137 (32.6%) of those patients receiving antiretroviral therapy at presentation. TB was culture-confirmed in 375 (53.4%) patients, 349 of which were first time treatment and 26 retreatment. Ten cases of isoniazid-resistant TB (2.9% of culture confirmed cases of newly treated TB), one of rifampin-resistant TB (0.3% culture confirmed cases of newly treated TB) and one of multi-drug resistant TB (MDR-TB) (3.8% of culture confirmed cases of retreatment TB) were detected. CONCLUSIONS: MDR-TB prevalence is low among outpatients initiating TB treatment in Lilongwe.