Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin.

BACKGROUND: Kaposi's sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique. METHODS: We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment. RESULTS: At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2-6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1-6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD. DISCUSSION: PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.

'I saw it as a second chance': A qualitative exploration of experiences of treatment failure and regimen change among people living with HIV on second- and third-line antiretroviral therapy in Kenya, Malawi and Mozambique.

Increasing numbers of people living with HIV (PLHIV) in sub-Saharan Africa are experiencing failure of first-line antiretroviral therapy and transitioning onto second-line regimens. However, there is a dearth of research on their treatment experiences. We conducted in-depth interviews with 43 PLHIV on second- or third-line antiretroviral therapy and 15 HIV health workers in Kenya, Malawi and Mozambique to explore patients' and health workers' perspectives on these transitions. Interviews were audio-recorded, transcribed and translated into English. Data were coded inductively and analysed thematically. In all settings, experiences of treatment failure and associated episodes of ill-health disrupted daily social and economic activities, and recalled earlier fears of dying from HIV. Transitioning onto more effective regimens often represented a second (or third) chance to (re-)engage with HIV care, with patients prioritising their health over other aspects of their lives. However, many patients struggled to maintain these transformations, particularly when faced with persistent social challenges to pill-taking, alongside the burden of more complex regimens and an inability to mobilise sufficient resources to accommodate change. Efforts to identify treatment failure and support regimen change must account for these patients' unique illness and treatment histories, and interventions should incorporate tailored counselling and social and economic support.

HIV-associated Kaposi's sarcoma in Maputo, Mozambique: outcomes in a specialized treatment center, 2010-2015.

BACKGROUND: Kaposi's sarcoma (KS) is a common HIV-associated malignancy associated with disability, pain and poor outcomes. The cornerstone of its treatment is antiretroviral therapy, but advanced disease necessitates the addition of chemotherapy. In high-income settings, this often consists of liposomal anthracyclines, but in Mozambique, the first line includes conventional doxorubicin, bleomycin and vincristine, which is poorly-tolerated. Médecins Sans Frontières supports the Ministry of Health (MOH) in a specialized HIV and KS treatment center at the Centro de Referencia de Alto Maé in Maputo. METHODS: We performed a retrospective analysis of data collected on patients enrolled at the CRAM between 2010 and 2015, extracting routinely-collected clinical information from patient care databases. KS treatment followed national guidelines, and KS staging followed AIDS Clinical Trials Group and MOH criteria. Baseline description of the cohort and patient outcomes was performed. Risk factors for negative outcomes (death or loss to follow-up) were explored using Cox regression. RESULTS: Between 2010 and 2015, 1573 patients were enrolled, and 1210 began chemotherapy. A majority were young adult males. At enrollment, CD4 was < 200 cells/µl in 45% of patients. Among patients receiving chemotherapy, 78% received combination doxorubicin-bleomycin-vincristine. Among patients receiving chemotherapy, 43% were lost to follow-up and 8% were known to have died. In multivariate regression, the only risk factors identified with poor outcomes were CD4 < 100 cells/µl at enrollment (Risk ratio 1.5, 95%CI 1.1-2.1, p = 0.02 and having S1 disease (RR 1.7, 95%CI 1.2-2.3, p = 0.001). DISCUSSION: We describe a large cohort of patients receiving care for HIV-associated KS in a specialized clinic in an urban setting. Outcomes were nonetheless unsatisfactory. Efforts should be made to decrease late referrals and entry into care and to increase access to more effective and better-tolerated treatments like liposomal doxorubicin.

An innovative system for 3D clinical photography in the resource-limited settings.

BACKGROUND: Kaposi's sarcoma (KS) is the most frequently occurring cancer in Mozambique among men and the second most frequently occurring cancer among women. Effective therapeutic treatments for KS are poorly understood in this area. There is an unmet need to develop a simple but accurate tool for improved monitoring and diagnosis in a resource-limited setting. Standardized clinical photographs have been considered to be an essential part of the evaluation. METHODS: When a therapeutic response is achieved, nodular KS often exhibits a reduction of the thickness without a change in the base area of the lesion. To evaluate the vertical space along with other characters of a KS lesion, we have created an innovative imaging system with a consumer light-field camera attached to a miniature "photography studio" adaptor. The image file can be further processed by computational methods for quantification. RESULTS: With this novel imaging system, each high-quality 3D image was consistently obtained with a single camera shot at bedside by minimally trained personnel. After computational processing, all-focused photos and measurable 3D parameters were obtained. More than 80 KS image sets were processed in a semi-automated fashion. CONCLUSIONS: In this proof-of-concept study, the feasibility to use a simple, low-cost and user-friendly system has been established for future clinical study to monitor KS therapeutic response. This 3D imaging system can be also applied to obtain standardized clinical photographs for other diseases.

Predictors of attrition and immunological failure in HIV-1 patients on highly active antiretroviral therapy from different healthcare settings in Mozambique.

In Mozambique, the evaluation of retention in HIV care and ART programmes is limited. To assess rate and predictors of attrition (no retention in care) and HAART effectiveness in HIV-1 infected patients who pay for medication and laboratory testing in Mozambique, we conducted a multicenter survey of HIV-1-infected patients who started HAART during 2002-2006. Cox proportional hazard models were used to assess risk of attrition and of therapy failure. Overall, 142 patients from 16 healthcare centers located in the capital city Maputo were followed-up for 22.2 months (12.1-46.7). The retention rate was 75%, 48% and 37% after one, two and three years, respectively. Risk of attrition was lower in patients with higher baseline CD4 count (P = 0.022) and attending healthcare center 1 (HCC1) (P = 0.013). The proportion of individuals with CD4 count ≤ 200 cells/µL was 55% (78/142) at baseline and decreased to 6% (3/52) at 36 months. Among the patients with available VL, 86% (64/74) achieved undetectable VL levels. The rate of immunologic failure was 17.2% (95% CI: 12.6-22.9) per 100 person-years. Risk of failure was associated to higher baseline CD4 count (P = 0.002), likely reflecting low adherence levels, and decreased with baseline VL ≥ 10,000 copies/mL (P = 0.033). These results suggest that HAART can be effective in HIV-1 infected patients from Mozambique that pay for their medication and laboratory testing. Further studies are required to identify the causes for low retention rates in patients with low CD4 counts and to better understand the association between healthcare setting and attrition rate.

Task shifting in Mozambique: cross-sectional evaluation of non-physician clinicians' performance in HIV/AIDS care.

BACKGROUND: Many resource-constrained countries now train non-physician clinicians in HIV/AIDS care, a strategy known as 'task-shifting.' There is as yet no evidence-based international standard for training these cadres. In 2007, the Mozambican Ministry of Health (MOH) conducted a nationwide evaluation of the quality of care delivered by non-physician clinicians (técnicos de medicina, or TMs), after a two-week in-service training course emphasizing antiretroviral therapy (ART). METHODS: Forty-four randomly selected TMs were directly observed by expert clinicians as they cared for HIV-infected patients in their usual worksites. Observed clinical performance was compared to national norms as taught in the course. RESULTS: In 127 directly observed patient encounters, TMs assigned the correct WHO clinical stage in 37.6%, and correctly managed co-trimoxazole prophylaxis in 71.6% and ART in 75.5% (adjusted estimates). Correct management of all 5 main aspects of patient care (staging, co-trimoxazole, ART, opportunistic infections, and adverse drug reactions) was observed in 10.6% of encounters.The observed clinical errors were heterogeneous. Common errors included assignment of clinical stage before completing the relevant patient evaluation, and initiation or continuation of co-trimoxazole or ART without indications or when contraindicated. CONCLUSIONS: In Mozambique, the in-service ART training was suspended. MOH subsequently revised the TMs' scope of work in HIV/AIDS care, defined new clinical guidelines, and initiated a nationwide re-training and clinical mentoring program for these health professionals. Further research is required to define clinically effective methods of health-worker training to support HIV/AIDS care in Mozambique and similarly resource-constrained environments.

Patterns of antibodies against latent and lytic antigens of human herpesvirus 8 in an endemic population and patients with Kaposi's sarcoma in Mozambique.

The patterns of antibodies against latent and lytic antigens of human herpesvirus 8 (HHV-8) were assessed using immunofluorescence assays of samples from 155 persons seropositive for HHV-8 seen at public health centers and 24 patients with Kaposi's sarcoma (KS) from Mozambique. Of the 155 persons without KS, 48 (31%) had antibodies against latent antigens only, 29 (18.7%) had antibodies against lytic antigens only, and 78 (50.3%) had antibodies against both types of antigen. The HHV-8 antibody titer tended to increase with age until age 40, after which it began to decrease. High titers of antibodies against latent and lytic antigens of HHV-8 were detected mostly in persons co-infected with HIV, and these increased titers could have a predictive value. All patients with KS except four patients who were seronegative for HHV-8 had elevated titers of HHV-8 antibodies, predominantly against latent antigens. The data suggest the potential for an increase in the development of KS in this endemic area for HHV-8.

Seroprevalence of human herpesvirus 8 infection in individuals from health care centers in Mozambique: potential for endemic and epidemic Kaposi's sarcoma.

Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its prevalence in Mozambique is unknown. The seroprevalence of HHV-8 in a cohort of individuals seen at public health centers in Northern (n = 208), Central (n = 226), or Southern (n = 318) Mozambique was examined. All individuals were interviewed to obtain socioeconomic, demographic and clinical data and were tested for serum anti-HHV-8 antibodies using an immunofluorescence assay. The overall frequency of HHV-8 antibodies was 21.4% and, in spite of the diversity of epidemiological characteristics of the tested individuals, did not differ significantly among regions: 18.7%, 24.3% and 21.4% in the North, Center, and South, respectively (chi(2), 2.37; P = 0.305). The variables that were associated significantly with the presence of HHV-8 antibodies were gender, age, level of education, number of siblings and HIV serostatus, but these differed across the regions. In the North, although tested individuals lived under poor socioeconomic conditions, no association between HHV-8 infection and household variables was detected, with the exception of the number of siblings (P = 0.042). In the Central region, HHV-8 infection was associated with gender (P = 0.010), the number of household members (P = 0.031), and the place of attendance (P = 0.021). In the South, HHV-8 infection was associated with the number of siblings (P = 0.023) and HIV status (P = 0.002). The overall prevalence of HHV-8 seropositivity increased with age. These results demonstrate that Mozambique is another country in Africa with endemic HHV-8 infection, and, because of the AIDS epidemic, continued access to antiretroviral treatment is necessary to avert an outbreak of AIDS-Kaposi's sarcoma.

Clinical staging of HIV-related illness in Mozambique: performance of nonphysician clinicians based on direct observation of clinical care and implications for health worker training.

INTRODUCTION: In Mozambique, clinical staging may be the primary determinant of HIV/AIDS treatment decisions, and the task of staging commonly falls to nonphysician clinicians (técnicos de medicina). Two years after the first Mozambican técnicos were trained in HIV/AIDS care, the quality of their performance in clinical staging was unknown. METHODS: Expert clinicians observed 127 clinical encounters conducted by a randomly selected national sample of 44 técnicos and compared observed clinical staging decisions to World Health Organization and Mozambican national norms. They also reviewed relevant Mozambican in-service training curricula in HIV/AIDS care. RESULTS: Observers agreed with fewer than half (44.1%) of the técnicos' stage-defining diagnoses. Misclassification or misdiagnosis of 3 complaints (weight loss, fever, and diarrhea) accounted for the majority of the observed errors. Review of health worker curricula determined that observed staging errors reflected content errors and omissions in the técnicos' in-service HIV/AIDS training and constraints in local laboratory and imaging capacity. DISCUSSION: In response to these findings, the Mozambican Ministry of Health has revised the técnicos' scope of work and has developed new guidelines, curriculum materials, and training strategies to improve the quality of clinical staging and opportunistic infection diagnosis in Mozambique.

Prevalence of human T-cell lymphotropic virus (HTLV-1/2) in individuals from public health centers in Mozambique.

The prevalence of human T-cell lymphotropic viruses types 1 and 2 (HTLV-1/2) in Mozambique is not known. The present study examined blood samples from 208, 226, and 318 individuals from Northern, Central, and Southern Mozambique, respectively, of all socioeconomic and demographic strata attending public health centers in Mozambique for HTLV-1/2-specific antibodies. Serum samples were assessed for HIV- and HTLV-1/2-specific antibodies by using enzyme immunoassays, and infections with HTLV-1 and -2 were confirmed by using Western blot. An overall HTLV-1/2 prevalence of 2.3% (2.9% in female and 1.1% in male subjects) was observed, and the prevalence of infection increased with age. Regional variation in the prevalence of HIV and HTLV-1/2 was observed; 32.2%, 65.5%, and 44% of individuals tested HIV positive in Northern, Central, and Southern Mozambique, respectively, and 2.4%, 3.9%, and 0.9% tested HTLV-1/2 positive in the same regions. HTLV-1 infection was confirmed in these individuals. No association between HTLV-1 infection and sociodemographic variables or HIV status was detected, although the low number of HTLV-1-positive cases did not allow robust statistical analyses. The results obtained suggest different risk factors and epidemiologic correlates of HIV and HTLV-1 transmission in Mozambique. Furthermore, our results suggested that North and Central Mozambique should be considered endemic regions for HTLV-1 infection. As no cases of HTLV-2 were detected, HTLV-2 appears to have not been introduced into Mozambique.

HIV-1 genetic diversity and transmitted drug resistance in health care settings in Maputo, Mozambique.

OBJECTIVES: To characterize HIV-1 diversity and transmitted drug resistance in persons with access to care and treatment in Maputo, Mozambique. METHODS: Samples were collected in 2002-2004 from 144 drug-naive patients attending public hospitals and private clinics. Plasma viremia, CD4, and CD8 cell counts were determined for each patient. The Stanford Algorithm was used for resistance genotyping on pol sequences. Subtyping was done by phylogenetic analysis. RESULTS: Most patients had high viral load (mean, 5.0 log copies/mL) and low CD4 cell counts (median, 260 CD4 cells/microL). Protease and/or reverse transcriptase sequences were obtained from 104 (72%) samples. Patients harbored subtypes C (80.8%), G (3.8%), CRF37_cpx (6.7%), untypable (U) (1.0%), and recombinant strains (7.7%) comprising the A, C, D, F, and U clades. There were no major protease inhibitor resistance mutations. Mutations conferring resistance to the nucleoside/nucleotide reverse transcriptase inhibitors and/or nonnucleoside reverse transcriptase inhibitors were found in 4 (4/68; 5.9%) patients. Phylogenetic analysis suggested an imported origin for 2 resistant variants. CONCLUSIONS: The HIV-1 epidemic in Maputo is evolving rapidly in genetic complexity due to the recent introduction of all major subtypes and recombinant forms. Continued surveillance of drug resistance in treated and untreated populations is needed to prevent further transmission of HIV drug-resistant variants and maximize the efficacy of antiretroviral therapy in Maputo.

First survey for detecting the presence of human herpesvirus 8 infection (HHV-8) in Maputo, Mozambique

Human herpesvirus 8 (HHV-8), the etiological agent of Kaposi's sarcoma (KS), is endemic in parts of the sub-Saharan, and KS has increased concomitantly with the HIV/AIDS epidemic. In Mozambique (MZ), no data concerning HHV-8 infection was available, thus the main of this work was to investigate, for the first time, the presence of HHV-8 infection in Maputo, MZ. Latent and lytic HHV-8-specific antibodies were assessed in blood samples from 189 individuals from the Central Hospital of Maputo, MZ, using "in-house" immunofluorescence assays conducted in São Paulo, Brazil. The results obtained were analyzed according to socio-demographic and clinical variables using the Chi-square test and logistic regression. An HHV-8 seropositivity of 1.8 percent and 9.7 percent was detected among 57 medical students and 31 individuals from the staff, respectively, in contrast to 16.4 percent detected among 67 out-patients. Concerning 34 hospitalized patients from the Dermatology Unit, 47.1 percent were HHV-8-seropositive overall, while the rate was 85.7 percent among KS patients. The present survey, conducted in Maputo, MZ, demonstrates great variation in HHV-8 infection frequencies depending on the group analyzed and epidemiological variables. An association between HHV-8 seropositivity and male gender (OR 5.72), the central origin of patients (OR 5.33), blood transfusions (OR 3.25), and KS (OR 24.0) was detected among hospitalized patients, and primary school (OR 7.18) and HIV-1 infection (OR 8.76) among out-patients.

First survey for detecting the presence of human herpesvirus 8 infection (HHV-8) in Maputo, Mozambique.

Human herpesvirus 8 (HHV-8), the etiological agent of Kaposi's sarcoma (KS), is endemic in parts of the sub-Saharan, and KS has increased concomitantly with the HIV/AIDS epidemic. In Mozambique (MZ), no data concerning HHV-8 infection was available, thus the main of this work was to investigate, for the first time, the presence of HHV-8 infection in Maputo, MZ. Latent and lytic HHV-8-specific antibodies were assessed in blood samples from 189 individuals from the Central Hospital of Maputo, MZ, using 'in-house' immunofluorescence assays conducted in São Paulo, Brazil. The results obtained were analyzed according to socio-demographic and clinical variables using the Chi-square test and logistic regression. An HHV-8 seropositivity of 1.8% and 9.7% was detected among 57 medical students and 31 individuals from the staff, respectively, in contrast to 16.4% detected among 67 out-patients. Concerning 34 hospitalized patients from the Dermatology Unit, 47.1% were HHV-8-seropositive overall, while the rate was 85.7% among KS patients. The present survey, conducted in Maputo, MZ, demonstrates great variation in HHV-8 infection frequencies depending on the group analyzed and epidemiological variables. An association between HHV-8 seropositivity and male gender (OR 5.72), the central origin of patients (OR 5.33), blood transfusions (OR 3.25), and KS (OR 24.0) was detected among hospitalized patients, and primary school (OR 7.18) and HIV-1 infection (OR 8.76) among out-patients.

Antiretroviral-associated toxicity among HIV-1-seropositive pregnant women in Mozambique receiving nevirapine-based regimens.

OBJECTIVE: To assess toxicities associated with highly active antiretroviral therapy (HAART) among HIV-1-infected pregnant women treated with nevirapine-based regimens according to Mozambican national guidelines. STUDY DESIGN: Prospective cohort study. METHODS: HIV-1-infected antiretroviral-naive pregnant women with CD4 counts < or =350 cells/microL were initiated on nevirapine, lamivudine, and stavudine or zidovudine and followed monthly. Severe hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > or =5-fold the upper limit of normal. Analyses were stratified by baseline CD4 count (<250 vs. 250-350 cells/microL). RESULTS: Among 146 pregnant women, 75 (52%) began nevirapine, lamivudine, and zidovudine and 71 (48%) began nevirapine, lamivudine, and stavudine. Overall, 79 (54%) women had CD4 counts <250 cells/microL, 7 (5%) had grade II hepatotoxicity, and 4 (3%) had severe (grade III or IV) hepatotoxicity. All 4 women with severe hepatotoxicity had baseline CD4 counts > or =250 cells/microL (P = 0.02). Rates of skin toxicity, anemia, and peripheral neuropathy did not differ by CD4 cell count group. Overall, 12 (8%) women changed or discontinued HAART as a result of drug toxicity. CONCLUSIONS: Severe hepatotoxicity from nevirapine-containing HAART in this cohort of pregnant women was more common at higher CD4 counts (6% vs. 0% among women with CD4 counts > or =250 cells/microL and CD4 counts <250 cells/microL, respectively), suggesting that laboratory monitoring is necessary when administering nevirapine-containing regimens to pregnant women with CD4 counts > or =250 cells/microL.