Providing HIV Treatment during community-wide flooding: experiences of clients and Health Care Workers in Malawi.

Background: In Malawi, community wide flooding, especially in high HIV burdened districts, continues to affect continuity of care and access to facilities. We explored the lived experiences of clients and healthcare workers (HCWs) to gain understanding of challenges and to propose interventions for improved ART care delivery. Methods: Participants came six health facilities and surrounding communities impacted by flooding between Dec 2021-Apr 2022 in Chikwawa, Nsanje and Mulanje districts in Malawi. Facilities are supported by Partners in Hope, a local NGO and PEPFAR/USAID partner.We conducted In-depth interviews with (IDIs) ART clients identified through medical chart reviews and focus group discussions (FGDs) with HCWs. IDIs and FGDs were coded using inductive and deductive methods in Atlas.ti. Results: We conducted IDIs with 23 respondents, of which, ten were women, ten experienced treatment interruption (>28 days without medication) and 17 relocated from their homes. The Six FGDs involved 37 HCWs. (21 ART providers; 16 lay cadre).In IDIs, most clients who relocated and lost livestock, possessions and ART medications. They travelling for income generation. Barriers to care included dangerous travel conditions, competing needs for time and fear of ill treatment at facilities. Some outreach clinics did not provide ART. Respondents were motivated to remain on care and motivators included fear of developing illnesses and HIV-status acceptance.All providers said that lack of standardized guidelines affected preparedness and response and they advocated for guidelines, stakeholder coordination and adequate resources. Most also reported personal physical exhaustion, damage to their own houses and property, and drug stock-outs. Documentation due to loss of registers was also mostly mentioned. Discussion: Clients motivated to remain in care but face barriers and challenges. National flooding protocols, adequate resource planning and seasonal 6-month ART dispensing may improve ART outcomes.

Prevention of mother-to-child transmission of HIV: a cross-sectional study in Malawi.

OBJECTIVE: To estimate the use and outcomes of the Malawian programme for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). METHODS: In a cross-sectional analysis of 33 744 mother-infant pairs, we estimated the weighted proportions of mothers who had received antenatal HIV testing and/or maternal antiretroviral therapy and infants who had received nevirapine prophylaxis and/or HIV testing. We calculated the ratios of MTCT at 4-26 weeks postpartum for subgroups that had missed none or at least one of these four steps. FINDINGS: The estimated uptake of antenatal testing was 97.8%; while maternal antiretroviral therapy was 96.3%; infant prophylaxis was 92.3%; and infant HIV testing was 53.2%. Estimated ratios of MTCT were 4.7% overall and 7.7% for the pairs that had missed maternal antiretroviral therapy, 10.7% for missing both maternal antiretroviral therapy and infant prophylaxis and 11.4% for missing maternal antiretroviral therapy, infant prophylaxis and infant testing. Women younger than 19 years were more likely to have missed HIV testing (adjusted odds ratio, aOR: 4.9; 95% confidence interval, CI: 2.3-10.6) and infant prophylaxis (aOR: 6.9; 95% CI: 1.2-38.9) than older women. Women who had never started maternal antiretroviral therapy were more likely to have missed infant prophylaxis (aOR: 15.4; 95% CI: 7.2-32.9) and infant testing (aOR: 13.7; 95% CI: 4.2-83.3) than women who had. CONCLUSION: Most women used the Malawian programme for the prevention of MTCT. The risk of MTCT increased if any of the main steps in the programme were missed.

Characteristics and outcomes of women initiating ART during pregnancy versus breastfeeding in Option B+ in Malawi.

BACKGROUND: Malawi adopted the PMTCT strategy 'Option B+' in 2011, providing life-long ART for all HIV-infected pregnant and breastfeeding women. We explored differences in characteristics and outcomes of women initiating ART during pregnancy versus breastfeeding. METHODS: We conducted a retrospective cohort analysis of women in Zomba District, southern Malawi, from January 2012- September 2013. Data were extracted from the Zomba District Observational Cohort Study, a surveillance project collecting data from standardized Ministry of Health ART monitoring tools. RESULTS: 1986 (67.2 %) women initiated ART during pregnancy and 969 (32.8 %) during breastfeeding. Women initiating ART in breastfeeding were more likely to be > 30 years (aOR = 1.33, 95 % CI1.11-1.59, p = 0.003) and have WHO Stage 3/4 (aOR = 2.74, 95 % CI1.94-3.87, p < 0.001). Eighteen (0.6 %) deaths occurred and 942 (31.9 %) women defaulted ART. 'Early' death (< 30 days) occurred in 3 (0.1 %) women and 449 (16.4 %) women defaulted early. Death/default < 30 days was more likely among women initiating ART during pregnancy (aOR 1.62, 95 % CI1.28-2.05, p < 0.001) or < 30 years old (aOR 1.27, 95 % CI 1.02-1.57, p = 0.03) and was less likely among those with WHO Stage 3/4 (aOR 0.30, 95 % CI 0.15-0.60, p < 0.001). Using Kaplan-Meier estimators to investigate time to death/default, we showed a sharp drop in death/default-free survival probability at time zero, yet survival probability decreased in a nearly linear manner after this initial period of high default. Women under 30 years had increased rates of death/default over time (log rank test: p < 0.001), however no significant differences were observed in death/default over time associated with timing of ART initiation, documented clinical stage at initiation, health clinic size or adherence rates. CONCLUSIONS: Many women in Malawi started ART during breastfeeding within Option B+ and were older and had more advanced WHO Clinical Staging. This represents a missed PMTCT opportunity to initiate treatment early in pregnancy. Early defaulting is identified as a challenge within Option B+, and was more likely among younger women and those initiating ART in pregnancy. Targeted research to understand factors associated with uptake of ART during pregnancy and retention in care could improve the efficacy of Option B+ in Malawi.

Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi.

Limited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/µl. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 µg/ml (2.474 to 5.596 µg/ml), area under the curve from 0 to 24 h (AUC0-∞) of 21.32 µg/ml · h (13.57 to 28.60 µg/ml · h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid, Cmax of 3.97 µg/ml (2.979 to 4.544 µg/ml), AUC0-24 of 22.5 (14.75 to 34.59 µg/ml · h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide, Cmax of 34.21 µg/ml (30.00 to 41.60 µg/ml), AUC0-24 of 386.6 µg/ml · h (320.0 to 463.7 µg/ml · h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol, Cmax of 2.278 µg/ml (1.694 to 3.098 µg/ml), AUC0-24 of 20.41 µg/ml · h (16.18 to 26.27 µg/ml · h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with those of other studies for all first-line drugs except for rifampin, for which the Cmax and AUC0-24 values were notably lower. Contrary to some earlier observations, HIV status did not significantly affect the AUC of any of the drugs. Increasing the dose of rifampin might be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in the half-life of isoniazid of 41% (P = 0.022). Possible competitive interactions between isoniazid and sulfamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further.

Screening HIV-infected adults in Malawi for anaemia: impact on eligibility for antiretroviral therapy.

Clinical staging determines antiretroviral therapy (ART) eligibility when CD4 count is not available. Haemoglobin (Hb) ≤8 g/dL is an indication for the treatment. We measured Hb in HIV-positive Malawian adults undergoing clinical assessment for ART eligibility and calculated the percentage of patients with CD4 ≤ 350 cells/µL deemed eligible for ART by clinical staging with and without Hb measurement, using the existing threshold and an alternative proposed after comparing Hb values to CD4 counts. Three hundred and thirty-eight patients had CD4 counts measured and 226 (67%) had CD4 ≤ 350 cells/µL. Thirty-six (16%) patients with low CD4 count were eligible for ART by clinical assessment alone, 48 (21%) when Hb was also measured with a threshold of ≤8 g/dL and 74 (34%) with a threshold of ≤10 g/dL. Measuring Hb alongside clinical assessment could increase the number of patients with CD4 ≤ 350 cells/µL starting ART by 33% using a threshold of Hb ≤ 8 g/dL or 114% with a threshold of ≤10g/dL.

HIV post-exposure prophylaxis programmes in the developed and developing world: can we learn from each other?

In an audit of HIV post-exposure prophylaxis (PEP) programmes in Blantyre, Malawi, and Liverpool, UK, a striking common deficiency was poor attendance of follow-up visits and of HIV testing to determine efficacy of PEP. Causes of poor follow-up after PEP need to be explored in both settings.

The prevalence of renal impairment among adults with early HIV disease in Blantyre, Malawi.

We determined the prevalence of renal impairment and possible HIV-associated nephropathy (HIVAN) in adults with World Health Organization (WHO) stages I or II HIV, presenting to the antiretroviral therapy (ART) clinic in a central hospital in Malawi. We enrolled 526 ART-naïve subjects, 67% women, median age 34 (17-73) years and mean CD4 count 305 (3-993) cells/µL. Blood pressure, weight, urine dipstick and microscopy, CD4 cell count and serum creatinine were measured. Creatinine clearance (CrCL) was estimated using the Cockcroft-Gault equation. Possible HIVAN was diagnosed based on levels of proteinuria and CrCl. In all, 23.3% had proteinuria (≥ 1+). 57.4% had reduced CrCl (< 90 mL/minute): 18.8% had moderate (CrCl 30-59 mL/minute) and 2.2% severe (CrCl <30 mL/minute) renal dysfunction. Extrapolating from renal biopsy studies that confirmed HIVAN, the proportion of patients with HIVAN in our clinic ranges from 1.8-21.2%. We conclude that renal impairment was common, though rarely severe, among HIV-infected adults with clinically non-advanced HIV disease. Renal dysfunction has been demonstrated to be a risk factor for (early) mortality. These results are relevant for ART programmes, such as those in Malawi, where renal function is not routinely assessed.

HIV testing coverage of family members of adult antiretroviral therapy patients in Malawi.

Many children in sub-Saharan Africa die from AIDS, not having accessed HIV testing and care. Children of adult antiretroviral therapy (ART) patients are a target group for HIV testing in order to increase access to care, but the HIV test coverage of this group in Malawi is unknown. In a cross-sectional survey of 832 patients at a large urban ART clinic in Blantyre, we found that 81.2% of 1223 children and 37.7% of 488 spouses of adult ART patients were reportedly not HIV tested. Wives of male patients were significantly less frequently HIV tested than husbands of female patients (53.0% vs. 72.4%, p<0.0001). Children under the age of 8 years (adjusted odds ratios [aOR] 2.76), children of female patients (aOR 2.53) and of patients whose partner had been HIV tested (aOR 2.87) were significantly more likely to have been tested for HIV. More attention needs to be given to provider initiated testing of children and spouses of ART patients.

Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection.

BACKGROUND: Few studies have investigated the impact of chronic hepatitis B and C infection on antiretroviral therapy (ART) outcomes in sub-Saharan Africa. Hepatotoxicity may be a particular concern in co-infected patients taking nevirapine-stavudine-lamivudine. METHODS: We conducted a prospective cohort study of 300 Malawian adults starting ART and describe one-year ART outcomes according to viral hepatitis status. RESULTS: At baseline, patients had advanced HIV disease (29.3% were in WHO stage 4; mean CD4 = 157 cells/microL; mean log(10)HIV-1 RNA = 5.24 copies/ml). Co-infection with hepatitis B, C and B + C were present in 6.7%, 5.7% and 1.7% respectively. At 50 weeks, all-cause mortality was 43 (14.3%). Sixteen (5.3%) had transferred to another unit. Eight (2.7%) were lost to follow up. Sixteen (5.3%) had stopped ART. 217 (72.3%) were alive on ART, of whom 82.5% had an HIV-1 RNA <400 copies/ml at week 50. During the first 50 weeks of ART, severe hepatotoxicity (liver enzyme values >5 times upper level of normal) occurred in 9%, but did not result in any ART discontinuations. Clinical hepatitis or jaundice was not observed. There were no significant differences in occurrence of hepatotoxicity, other side effects, mortality, severe morbidity, immune reconstitution or virological failure between hepatitis B and/or C co-infected patients and those who were not. Viral hepatitis co-infection was not associated with severe hepatotoxicity, mortality, severe morbidity or virological failure in multivariate analyses. CONCLUSION: Our data suggest that screening for viral hepatitis B and C and liver enzyme monitoring may not require high priority in ART programmes in sub-Saharan Africa.

High prevalence of suspected HIV-associated dementia in adult Malawian HIV patients.

HIV-associated dementia (HAD) has received little attention in sub-Saharan Africa, and there are no data available from Malawi. We used the International HIV Dementia Scale (IHDS), a cross-cultural, simple and validated screening tool to study the prevalence of suspected HAD, defined as an IHDS score

Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline.

OBJECTIVES: The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi. METHODS: Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV-1 RNA copies/mL) and, if failure was confirmed, initiated on second-line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months. RESULTS: Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second-line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV-related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV-1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/microL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14-10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15-17.12) were risk factors for death. Baseline CD4 count <50 cells/microL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01-6.52). CONCLUSIONS: Second-line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.

Reliability of rapid testing for hepatitis B in a region of high HIV endemicity.

Hepatitis B (HBV) and HIV co-infection is common in resource-poor settings. A recent study from Malawi revealed poor correlation between hepatitis B surface antigen (HBsAg) point-of-care tests and reference tests in patients co-infected with HIV. We studied a cohort of 300 Malawian adults entering a treatment programme for HIV. Sera were tested for HBsAg first using the Determine rapid test and re-tested using a commercial enzyme immunoassay (EIA). All tests were done under optimal conditions in Liverpool, UK. Sera from all 25 patients positive for HBsAg using the rapid test and from 50 who were negative, were re-tested using the EIA, with complete concordance of results. The kappa correlation was 1, specificity 100% (93-100%) and sensitivity 100% (86-100%) compared to the reference test. Patients had advanced immune suppression (mean CD4=175 cells x 10(6)/l). In a non-field setting, the results of point-of-care Determine rapid hepatitis B tests appear reliable in patients with HIV-1 co-infection.

Hypoadrenalism is not associated with early mortality during tuberculosis treatment in Malawi.

SETTING: In the developing world, early mortality within 1 month of commencing tuberculosis (TB) treatment is high, particularly with human immunodeficiency virus (HIV) co-infection. In Malawi, 40% of those who die do so in the first month of treatment. Reasons remain unclear and may include delayed diagnosis, opportunistic infections, immune restoration inflammatory syndrome (IRIS) or malnutrition. One possible contributing factor is underlying hypoadrenalism associated with TB-HIV, exacerbated by rifampicin (RMP) induction of P450 and glucocorticoid metabolism. OBJECTIVE: To assess the prevalence of hypoadrenalism in TB patients before and after commencement of TB treatment, and relationship with early mortality. DESIGN: Prospective descriptive study assessing hypoadrenalism before and after anti-tuberculosis treatment, HIV status and outcome up to 3 months post-treatment. RESULTS: Of 51 patients enrolled, 29 (56.9%) were female (median age 32 years, range 18-62). Of 43 patients HIV-tested, 38 (88.3%) were HIV-positive and 15.7% died within the first month. At 3 months, 11 (21.6%) were known to have died. Adequate cortisol levels were found in 49/51 (95.9%) before commencing RMP. Neither of the two with reduced response died. All 34 patients revealed adequate cortisol responses at 2 weeks. CONCLUSION: No evidence of hypoadrenalism was found in this first study to assess adrenal function and outcome of anti-tuberculosis treatment.

[The introduction of antiretroviral therapy in Malawi]. / De introductie van antiretrovirale therapie in Malawi.

The prevalence of HIV infection in Malawi is high. Until mid 2004, antiretroviral therapy (ART) was only available for a fee; later, a programme for free distribution was started. When ART was started, no laboratory tests other than an HIV test were felt to be necessary. After an introductory period in which hospitals were assessed for the presence of sufficient infrastructure and health workers were trained in ART, the number of public and private clinics where ART was distributed rose to 60. By end 2005, the number of patients on ART was 37,840, which is 45% of the target in the so-called '3-by-5' initiative of the WHO/Joint United Nations Programme on HIV/ AIDS (UNAIDS). The goal of this initiative was to have half (85,000) ofthe estimated 170,000 HIV-infected individuals in Malawi for whom ART is indicated on treatment by end 2005. After 12 months of follow-up, 81% of the patients treated were still alive and on treatment, while the mortality was 10%, 8% no longer visited the outpatient clinic, and 1% had stopped ART. Despite facing various challenges, intensive collaboration with all stakeholders involved, under strong leadership of the Ministry of Health, has laid the foundation for this thus far successful programme.

Evaluation of antiretroviral therapy results in Blantyre, Malawi.

UNLABELLED: We performed a cross sectional study to evaluate treatment results of the paying antiretroviral therapy clinic of Queen Elizabeth Central Hospital, Blantyre. The only antiretroviral therapy was a fixed drug combination of stavudine, lamivudine and nevirapine. METHODS: Interviews, laboratory tests (CD4 count, viral load, nevirapine plasma levels, transaminases) and data extraction from files. 422 (59 %) of the patients who started antiretroviral therapy since 2000 were lost to follow up. The 176 patients enrolled in the study had good virological and excellent clinical treatment results. The most common side effect was peripheral neuropathy. Nevirapine plasma levels were remarkably high and associated with successful virological treatment results. Two simple adherence questions pertaining to the use of medication in the previous 8 days corresponded well with nevirapine levels. The most important reasons for non-adherence were shortage of drugs in the hospital pharmacy and personal financial constraints. CONCLUSIONS: Many patients were lost to follow up.High nevirapine levels contributed to good therapy results in those studied.Simple adherence questions predicted sub-therapeutic nevirapine levels.Antiretroviral drug supply needs to be uninterrupted and free of charge, to prevent avoidable non-adherence.

[Tuberculosis and HIV coinfection in three patients: the possibilities for simultaneous treatment]. / Tuberculose- en HIV-co-infectie bij 3 patiënten: mogelijkheden voor gelijktijdige behandeling.

Three patients received simultaneous treatment for tuberculosis and HIV: a 23-year-old woman and a 33-year-old man who were asylum seekers from Africa and a 45-year-old woman who was an intravenous drug addict. During the treatment with antiretroviral and anti-tuberculous drugs, several problems arose: drug interactions (between rifampicine and protease inhibitors/non-nucleoside reverse transcriptase inhibitors), side effects, non-compliance and immune reconstitution reactions. These problems were solved either by temporary withdrawal of the medication or by substituting other drugs. There are a number of possible treatment strategies that minimise the risks. Despite the potential problems, in patients with advanced HIV infection, antiretroviral treatment should not be delayed until after the end of the tuberculosis treatment.

Pharmacokinetics, food intake requirements and tolerability of once-daily combinations of nelfinavir and low-dose ritonavir in healthy volunteers.

AIMS: This study was performed to evaluate the steady-state pharmacokinetics, food intake requirements and short-term tolerability of once-daily combinations of nelfinavir and low-dose ritonavir. METHODS: Twenty-seven healthy volunteers were randomized over three groups to receive a once-daily regimen of nelfinavir/ritonavir 2,000/200 mg (group 1), 2,000/400 mg (group 2) or 2,500/200 mg (group 3) with food for 14 days. Pharmacokinetic parameters for nelfinavir and its active metabolite M8 were assessed on study days 15 and 16, after administration of the regimens with a full (610 kcal) or light (271 kcal) breakfast, respectively. RESULTS: Pharmacokinetic data were evaluable for eight volunteers in group 1, eight in group 2 and four in group 3. Administration of nelfinavir/ritonavir with a full breakfast resulted in geometric mean (GM) nelfinavir AUC(24h) values of 76.8, 51.3, and 61.9 h*mg/l in group 1, 2 and 3, respectively. GM 24-h Cmin concentrations of nelfinavir were 0.76 mg l(-1), 0.43 mg l(-1) and 0.47 mg l(-1), respectively. Co-administration of ritonavir increased M8 concentrations more than nelfinavir concentrations, resulting in GM AUC(24h) and Cmin values for nelfinavir plus M8 that were higher than or comparable to reference values for the approved regimen of nelfinavir (1,250 mg BID without ritonavir). In the 2,000/200 mg group, seven out of eight subjects had a Cmin value of nelfinavir plus M8 above a threshold of 1.0 mg l-1. Administration of the combinations with a light breakfast resulted in significant decreases in the AUC(24h) and Cmin of nelfinavir and nelfinavir plus M8, compared with intake with a full breakfast. For the Cmin of nelfinavir plus M8, the GM ratio (light/full breakfast) was 0.76 (90% confidence interval 0.67-0.86, participants from all groups combined). Short-term tolerability was satisfactory, apart from a higher than expected incidence of mild rash (12%). CONCLUSIONS: Administration of nelfinavir in a once-daily regimen appears feasible. A nelfinavir/ritonavir 2,000/200 mg combination appears appropriate for further evaluation. Once-daily nelfinavir/ritonavir should be taken with a meal containing at least 600 kcal.