Browsing by Author "Kankasa C"

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Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission.
(2008-Jun-01) Chi BH; Chintu N; Cantrell RA; Kankasa C; Kruse G; Mbewe F; Sinkala M; Smith PJ; Stringer EM; Stringer JS
OBJECTIVE: To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. METHODS: In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. RESULTS: Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). CONCLUSIONS: Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.
Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia.
(2007-Oct-24) Bolton-Moore C; Mubiana-Mbewe M; Cantrell RA; Chintu N; Stringer EM; Chi BH; Sinkala M; Kankasa C; Wilson CM; Wilfert CM; Mwango A; Levy J; Abrams EJ; Bulterys M; Stringer JS
CONTEXT: The Zambian Ministry of Health provides pediatric antiretroviral therapy (ART) at primary care clinics in Lusaka, where, despite scale-up of perinatal prevention efforts, many children are already infected with the human immunodeficiency virus (HIV). OBJECTIVE: To report early clinical and immunologic outcomes of children enrolled in the pediatric treatment program. DESIGN, SETTING, AND PATIENTS: Open cohort assessment using routinely collected clinical and outcome data from an electronic medical record system in use at 18 government primary health facilities in Lusaka, Zambia. Care was provided primarily by nurses and clinical officers ("physician extenders" akin to physician assistants in the United States). Patients were children (<16 years of age) presenting for HIV care between May 1, 2004, and June 29, 2007. INTERVENTION: Three-drug ART (zidovudine or stavudine plus lamivudine plus nevirapine or efavirenz) for children who met national treatment criteria. MAIN OUTCOME MEASURES: Survival, weight gain, CD4 cell count, and hemoglobin response. RESULTS: After enrollment of 4975 children into HIV care, 2938 (59.1%) started ART. Of those initiating ART, the median age was 81 months (interquartile range, 36-125), 1531 (52.1%) were female, and 2087 (72.4%) with World Health Organization stage information were in stage III or IV. At the time of analysis, 158 children (5.4%) had withdrawn from care and 382 (13.0%) were at least 30 days late for follow-up. Of the remaining 2398 children receiving ART, 198 (8.3%) died over 3018 child-years of follow-up (mortality rate, 6.6 deaths per 100 child-years; 95% confidence interval [CI], 5.7-7.5); of these deaths, 112 (56.6%) occurred within 90 days of therapy initiation (early mortality rate, 17.4/100 child-years; post-90-day mortality rate, 2.9/100 child-years). Mortality was associated with CD4 cell depletion, lower weight-for-age, younger age, and anemia in multivariate analysis. The mean CD4 cell percentage at ART initiation among the 1561 children who had at least 1 repeat measurement was 12.9% (95% CI, 12.5%-13.3%) and increased to 23.7% (95% CI, 23.1%-24.3%) at 6 months, 27.0% (95% CI, 26.3%-27.6%) at 12 months, 28.0% (95% CI, 27.2%-28.8%) at 18 months, and 28.4% (95% CI, 27.4%-29.4%) at 24 months. CONCLUSIONS: Care provided by clinicians such as nurses and clinical officers can result in good outcomes for HIV-infected children in primary health care settings in sub-Saharan Africa. Mortality during the first 90 days of therapy is high, pointing to a need for earlier intervention.
Deciphering Early Childhood Infection by the Kapsosi's sarcoma Associated Human Herpesvirus in Zambia
(2012-3-31) Minhas V; Kankasa C; Crabtree K; Gondwe C; Wood C
Human herpesviruses are large double-stranded DNA viruses that are ubiquitous in nature. There are currently eight known human herpesviruses belonging to three subfamilies: alpha, beta and gamma herpesvirinae. They were subdivided based on morphology, biological properties, genome structure and sequence homology. Human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the most recently described human herpesvirus. HHV-8 was co-discovered by Chang and Moore in 1994, from lesions of a Kaposi's sarcoma (KS) patient by representational differential analysis. HHV-8 DNA sequences in the KS tissue, which were not found in normal skin tissue, could then be amplified. Human herpesvirus-8 (HHV-8) is the infectious etiologic agent of all forms of Kaposi's sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease. KS is an AIDS-defining illness and is the most common malignancy present in HIV infected patients. During the early stages of the AIDS epidemic, KS was the most common AIDS-defining illness. In fact, it was the sudden appearance of Kaposi's sarcoma (KS) and shortly thereafter, the appearance of high-grade non-Hodgkin's lymphoma (NHL) in a handful of young homosexual men who otherwise were in good health signalled the start of the AIDS epidemic. Due to the ongoing HIV epidemic in sub-Saharan Africa, KS has become one of the most frequently diagnosed cancers in this region. Global seroprevalence of HHV-8 varies greatly and is generally high in areas where non-HIV associated forms of KS (classic or endemic forms) have been common. HHV-8 seroprevalence in the United States and Northern Europe is generally low but ranges from 20 to 80 percent in adult populations in Africa and Mediterranean regions. Zambia is a part of the “KS belt” where endemic KS was prevalent and where a significant increase in KS incidence in adults and children has coincided with the emergence of the HIV-1 epidemic. By 1992, KS accounted for approximately 25% of all childhood cancers diagnosed in Lusaka, the capital of Zambia. The modes of transmission of HHV-8 may be different in different parts of the world depending on the endemicity of that region and are still being investigated but both horizontal and vertical transmission has been reported. Horizontal transmission via heterosexual and homosexual contact has been reported in adults. Vertical transmission to children seems to occur at a very low rate; a likely source of non-sexual transmission is via saliva, and rare transmission may occur also through breast milk. A report from Uganda has provided evidence for HHV-8 transmission through blood transfusion. HHV-8 can be found in the PBMCs, saliva, oropharyngeal mucosa, semen and prostate glands which represent the source of both vertical and horizontal transmission.Human herpesviruses are large double-stranded DNA viruses that are ubiquitous in nature. There are currently eight known human herpesviruses belonging to three subfamilies: alpha, beta and gamma herpesvirinae. They were subdivided based on morphology, biological properties, genome structure and sequence homology. Human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the most recently described human herpesvirus. HHV-8 was co-discovered by Chang and Moore in 1994, from lesions of a Kaposi's sarcoma (KS) patient by representational differential analysis. HHV-8 DNA sequences in the KS tissue, which were not found in normal skin tissue, could then be amplified. Human herpesvirus-8 (HHV-8) is the infectious etiologic agent of all forms of Kaposi's sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease. KS is an AIDS-defining illness and is the most common malignancy present in HIV infected patients. During the early stages of the AIDS epidemic, KS was the most common AIDS-defining illness. In fact, it was the sudden appearance of Kaposi's sarcoma (KS) and shortly thereafter, the appearance of high-grade non-Hodgkin's lymphoma (NHL) in a handful of young homosexual men who otherwise were in good health signalled the start of the AIDS epidemic. Due to the ongoing HIV epidemic in sub-Saharan Africa, KS has become one of the most frequently diagnosed cancers in this region. Global seroprevalence of HHV-8 varies greatly and is generally high in areas where non-HIV associated forms of KS (classic or endemic forms) have been common. HHV-8 seroprevalence in the United States and Northern Europe is generally low but ranges from 20 to 80 percent in adult populations in Africa and Mediterranean regions. Zambia is a part of the “KS belt” where endemic KS was prevalent and where a significant increase in KS incidence in adults and children has coincided with the emergence of the HIV-1 epidemic. By 1992, KS accounted for approximately 25% of all childhood cancers diagnosed in Lusaka, the capital of Zambia. The modes of transmission of HHV-8 may be different in different parts of the world depending on the endemicity of that region and are still being investigated but both horizontal and vertical transmission has been reported. Horizontal transmission via heterosexual and homosexual contact has been reported in adults. Vertical transmission to children seems to occur at a very low rate; a likely source of non-sexual transmission is via saliva, and rare transmission may occur also through breast milk. A report from Uganda has provided evidence for HHV-8 transmission through blood transfusion. HHV-8 can be found in the PBMCs, saliva, oropharyngeal mucosa, semen and prostate glands which represent the source of both vertical and horizontal transmission.
Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine.
(2007-May-11) Chi BH; Sinkala M; Stringer EM; Cantrell RA; Mtonga V; Bulterys M; Zulu I; Kankasa C; Wilfert C; Weidle PJ; Vermund SH; Stringer JS
OBJECTIVE: To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI). METHODS: Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines. RESULTS: Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7). CONCLUSION: Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.
Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia.
(2005-Aug-12) Stringer JS; Sinkala M; Maclean CC; Levy J; Kankasa C; Degroot A; Stringer EM; Acosta EP; Goldenberg RL; Vermund SH
OBJECTIVE: To determine the population effectiveness of a city-wide perinatal HIV prevention program. DESIGN: An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP). METHODS: All 10 public-sector delivery centers in Lusaka, Zambia participated. All mother-infant pairs delivering during the 12-week surveillance period at the participating centers and who received antenatal care at a public-sector facility in Lusaka were included in the study. The main outcome measure was population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the population that ingested NVP. RESULTS: Of 8787 women in the surveillance population, 7204 (82%) had been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers (90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother-infant pairs in the surveillance population received both a maternal and infant dose of NVP. CONCLUSIONS: Successful perinatal HIV prevention requires each mother-infant pair to negotiate a cascade of events that begins with offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance demonstrates that failures occur at each step, resulting in reduced coverage and diminished program effectiveness.
Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial.
(2007-Nov-17) Chi BH; Sinkala M; Mbewe F; Cantrell RA; Kruse G; Chintu N; Aldrovandi GM; Stringer EM; Kankasa C; Safrit JT; Stringer JS
BACKGROUND: Intrapartum and neonatal single-dose nevirapine are essential components of perinatal HIV prevention in resource-constrained settings, but can induce resistance to other non-nucleoside reverse transcriptase inhibitor drugs. We aimed to investigate whether this complication would be reduced with a single peripartum intervention of tenofovir and emtricitabine. METHODS: We randomly assigned 400 HIV-infected pregnant women who sought care at two public-sector primary health facilities in Lusaka, Zambia. One was excluded, 200 were assigned to receive a single oral dose of 300 mg tenofovir disoproxil fumarate with 200 mg emtricitabine under direct observation, and 199 to receive no study drug. Short-course zidovudine and intrapartum nevirapine were offered to all HIV-infected women, according to the local standard of care. Women who met national criteria for antiretroviral therapy were referred for care and not enrolled. Our primary study outcome was resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery. We used standard population sequencing to determine HIV genotypes. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00204308. FINDINGS: Of the 200 women who were randomly assigned to the intervention, 14 were lost to follow-up or withdrew from the study, two did not take study drug according to protocol, and one specimen was lost; 23 of 199 controls were lost to follow-up or withdrew from the study, and three specimens were lost. Women given the intervention were 53% less likely than controls to have a mutation that conferred resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery (20/173 [12%] vs 41/166 [25%]; risk ratio [RR] 0.47, 95% CI 0.29-0.76). We noted postpartum anaemia, the most common serious adverse event in mothers, in four women in each group. 20 of 198 (10%) infants in the intervention group and 23 of 199 (12%) controls had a serious adverse event, mostly due to septicaemia (n=22) or pneumonia (n=8); these events did not differ between groups, and none were judged to be caused by the study intervention. INTERPRETATION: A single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; therefore this treatment should be considered as an adjuvant to intrapartum nevirapine.