This report documents the feasibility of effective antiretroviral therapy in a large number of patients in an impoverished country. Overall, the outcomes are similar to those in the United States. These results provide evidence in support of international efforts to make antiretroviral therapy available to patients with AIDS in developing countries.
Background. Data are limited about the effectiveness of pediatric antiretroviral therapy (ART) in low-income countries.Methods. We report the outcomes of consecutively treating 236 human immunodeficiency virus type 1 (HIV-1)-infected treatment-naive children with triple ART in Port-au-Prince, Haiti, between 1 May 2003 and 30 April 2006.Results. Kaplan-Meier survival analysis at follow-up demonstrated that 191 children (81%) remained in care, 21 (9%) were dead, and 24 (10%) were lost to follow-up. Independent baseline predictors of mortality were age !18 months, CD4 + T cell percentage р5%, and weight-for-age Z score (WAZ) less than Ϫ3. Twelve months into ART, 56% of tested subjects had undetectable HIV-1 RNA loads. Median CD4 + T cell percentages at 12 months increased by 15%, 11%, and 5% in children with baseline percentages of р5%, 6%-24%, and у25%, respectively ( ). The median WAZ at 12 months increased by 1.0, 0.6, and 0.2 in children with baseline WAZ less than P ! .01 Ϫ2, Ϫ2 to Ϫ1.1, and Ϫ1 or more, respectively ( ). P ! .01 Conclusion. With continuous donor support, trained providers, and the availability of pediatric antiretroviral drug formulations, it proved feasible to deliver pediatric ART in Haiti. The effectiveness of this program should encourage efforts to make ART available for HIV-infected children in poor countries.
Expression of HLA-B57 is associated with restricted replication of human immunodeficiency virus (HIV), but the mechanism for its protective effect remains unknown. If this advantage depends upon CD8 T-cell recognition of B57-restricted epitopes, mother-to-child transmission of escape mutations within these epitopes could nullify its protective effect. However, if the B57 advantage is largely mediated by selection for fitnessattenuating viral mutations within B57-restricted epitopes, such as T242N in TW10-Gag, then the transmission of such mutations could facilitate viral control in the haploidentical infant. We assessed the consequences of B57-associated mutations on replication capacity, viral control, and clinical outcome after vertical transmission in 13 mother-child pairs. We found that expression of HLA-B57 was associated with exceptional control of HIV during infancy, even when mutations within TW10 and most other B57-restricted epitopes were transmitted, subverting the natural immunodominance of HLA-B57. In contrast, most B57-negative infants born to B57-positive mothers progressed rapidly to AIDS. The presence of T242N led to a reproducible reduction in viral fitness, as demonstrated by in vitro assays using NL4-3 constructs encoding p24 sequences from individual mothers and infants. Associated compensatory mutations within p24-Gag were observed to reverse this impairment and to influence the propensity of T242N to revert after transmission to B57-negative hosts. Moreover, primary failure to control viremia was observed in one infant to whom multiple compensatory mutations were transmitted along with T242N. These parallel in vivo and in vitro data suggest that HLA-B57 confers its advantage primarily by driving and maintaining a fitness-attenuating mutation in p24-Gag.
This report demonstrates the feasibility, demand, and effective synergy of integrating on-site primary care services into HIV VCT in Haiti. VCT is a good entry point for people in need of services for communicable diseases and reproductive health, and, reciprocally, services attract more people to VCT, including populations that are at high risk for HIV infection. This program is being duplicated elsewhere in Haiti and can serve as a model for other countries.
BackgroundThe ability to accurately determine respiratory muscle strength is vitally important in patients with neuromuscular disorders (NMD). Sniff nasal inspiratory pressure (SNIP), a test of inspiratory muscle strength, is easier to perform for many NMD patients than the more commonly used determination of maximum inspiratory pressure measured at the mouth (MIP). However, due to an inconsistent approach in the literature, the optimal technique to perform the SNIP maneuver is unclear. Therefore, we systematically evaluated the impact of performing the maneuver with nostril contralateral to the pressure-sensing probe open (SNIPOP) versus closed (SNIPCL), on determination of inspiratory muscle strength in NMD patients as well as control subjects with normal respiratory muscle function.MethodsNMD patients (n = 52) and control subjects without respiratory dysfunction (n = 52) were studied. SNIPOP, SNIPCL, and MIP were measured during the same session and compared using ANOVA. Agreement and bias were assessed with intraclass correlation coefficients (ICC) and Bland-Altman plots.ResultsMean MIP values were 58.2 and 94.0 cmH2O in NMD and control subjects, respectively (p<0.001). SNIPCL was greater than SNIPOP in NMD (51.9 ±31.0 vs. 36.9 ±25.4 cmH2O; p<0.001) as well as in controls (89.2 ±28.1 vs. 69.2 ±29.2 cmH2O; p<0.001). In both populations, the ICC between MIP and SNIPCL (NMD = 0.78, controls = 0.35) was higher than for MIP and SNIPOP (NMD = 0.53, controls = 0.06). In addition, SNIPCL was more often able to exclude inspiratory muscle weakness than SNIPOP.ConclusionsSNIPCL values are systematically higher than SNIPOP in both normal subjects and NMD patients. Therefore, SNIPCL is a useful complementary test for ruling out inspiratory muscle weakness in individuals with low MIP values.
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